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Sample records for high basal activity

  1. Basal Forebrain Gating by Somatostatin Neurons Drives Prefrontal Cortical Activity.

    Science.gov (United States)

    Espinosa, Nelson; Alonso, Alejandra; Morales, Cristian; Espinosa, Pedro; Chávez, Andrés E; Fuentealba, Pablo

    2017-11-17

    The basal forebrain provides modulatory input to the cortex regulating brain states and cognitive processing. Somatostatin-expressing neurons constitute a heterogeneous GABAergic population known to functionally inhibit basal forebrain cortically projecting cells thus favoring sleep and cortical synchronization. However, it remains unclear if somatostatin cells can regulate population activity patterns in the basal forebrain and modulate cortical dynamics. Here, we demonstrate that somatostatin neurons regulate the corticopetal synaptic output of the basal forebrain impinging on cortical activity and behavior. Optogenetic inactivation of somatostatin neurons in vivo rapidly modified neural activity in the basal forebrain, with the consequent enhancement and desynchronization of activity in the prefrontal cortex, reflected in both neuronal spiking and network oscillations. Cortical activation was partially dependent on cholinergic transmission, suppressing slow waves and potentiating gamma oscillations. In addition, recruitment dynamics was cell type-specific, with interneurons showing similar temporal profiles, but stronger responses than pyramidal cells. Finally, optogenetic stimulation of quiescent animals during resting periods prompted locomotor activity, suggesting generalized cortical activation and increased arousal. Altogether, we provide physiological and behavioral evidence indicating that somatostatin neurons are pivotal in gating the synaptic output of the basal forebrain, thus indirectly controlling cortical operations via both cholinergic and non-cholinergic mechanisms. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. Basal blood parameters of horses subjected to aerobic activity fed with lipidic concentrated

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    Kátia de Oliveira

    2012-02-01

    Full Text Available The feeding diets were evaluated containing low and high levels of soybean oil for horses athletes subjected to two protocols of aerobic training on the response of basal blood biochemical parameters. Four horses were used in latin square design with treatments in a 2 x 2 factorial arrangement. Treatments consisted levels of 5 and 15% oil concentrates and two aerobic training, 40' and 60' minutes. Plasmatic parameters were monitored, triglyceride (TG, total cholesterol (TC, glucose (GLU and lactate (LAC, during basal metabolism. The TG, TC, GLU and LAC from horses at rest were not affected (P> 0.05 neither of diet and physical activity, 0.21, 3.79, 4.18, 0.93 mmol L-1, respectively. It can be concluded that offer concentrate with high content of soybean oil to athletic horses in aerobic activities can be performed without altering the blood biochemical profile of basal metabolism.

  3. Oscillatory activity in the basal ganglia and deep brain stimulation.

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    Guridi, Jorge; Alegre, Manuel

    2017-01-01

    Over the past 10 years, research into the neurophysiology of the basal ganglia has provided new insights into the pathophysiology of movement disorders. The presence of pathological oscillations at specific frequencies has been linked to different signs and symptoms in PD and dystonia, suggesting a new model to explain basal ganglia dysfunction. These advances occurred in parallel with improvements in imaging and neurosurgical techniques, both of which having facilitated the more widespread use of DBS to modulate dysfunctional circuits. High-frequency stimulation is thought to disrupt pathological activity in the motor cortex/basal ganglia network; however, it is not easy to explain all of its effects based only on changes in network oscillations. In this viewpoint, we suggest that a return to classic anatomical concepts might help to understand some apparently paradoxical findings. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

  4. Dual-Native Vacancy Activated Basal Plane and Conductivity of MoSe2 with High-Efficiency Hydrogen Evolution Reaction.

    Science.gov (United States)

    Gao, Daqiang; Xia, Baorui; Wang, Yanyan; Xiao, Wen; Xi, Pinxian; Xue, Desheng; Ding, Jun

    2018-04-01

    Although transition metal dichalcogenide MoSe 2 is recognized as one of the low-cost and efficient electrocatalysts for the hydrogen evolution reaction (HER), its thermodynamically stable basal plane and semiconducting property still hamper the electrocatalytic activity. Here, it is demonstrated that the basal plane and edges of 2H-MoSe 2 toward HER can be activated by introducing dual-native vacancy. The first-principle calculations indicate that both the Se and Mo vacancies together activate the electrocatalytic sites in the basal plane and edges of MoSe 2 with the optimal hydrogen adsorption free energy (ΔG H* ) of 0 eV. Experimentally, 2D MoSe 2 nanosheet arrays with a large amount of dual-native vacancies are fabricated as a catalytic working electrode, which possesses an overpotential of 126 mV at a current density of 100 mV cm -2 , a Tafel slope of 38 mV dec -1 , and an excellent long-term durability. The findings pave a rational pathway to trigger the activity of inert MoSe 2 toward HER and also can be extended to other layered dichalcogenide. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Effects of high fat diet on the Basal activity of the hypothalamus-pituitary-adrenal axis in mice: a systematic review.

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    Auvinen, H E; Romijn, J A; Biermasz, N R; Havekes, L M; Smit, J W A; Rensen, P C N; Pereira, A M

    2011-12-01

    Hypothalamus-pituitary-adrenal-axis activity is suggested to be involved in the pathophysiology of the metabolic syndrome. In diet-induced obesity mouse models, features of the metabolic syndrome are induced by feeding high fat diet. However, the models reveal conflicting results with respect to the hypothalamus-pituitary-adrenal-axis activation. The aim of this review was to assess the effects of high fat feeding on the activity of the hypothalamus-pituitary-adrenal-axis in mice. PubMed, EMBASE, Web of Science, the Cochrane database, and Science Direct were electronically searched and reviewed by 2 individual researchers. We included only original mouse studies reporting parameters of the hypothalamus-pituitary-adrenal-axis after high fat feeding, and at least 1 basal corticosterone level with a proper control group. Studies with adrenalectomized mice, transgenic animals only, high fat diet for less than 2 weeks, or other interventions besides high fat diet, were excluded. 20 studies were included. The hypothalamus-pituitary-adrenal-axis evaluation was the primary research question in only 5 studies. Plasma corticosterone levels were unchanged in 40%, elevated in 30%, and decreased in 20% of the studies. The effects in the peripheral tissues and the central nervous system were also inconsistent. However, major differences were found between mouse strains, experimental conditions, and the content and duration of the diets. This systematic review demonstrates that the effects of high fat feeding on the basal activity of the hypothalamus-pituitary-adrenal-axis in mice are limited and inconclusive. Differences in experimental conditions hamper comparisons and accentuate the need for standardized evaluations to discern the effects of diet-induced obesity on the hypothalamus-pituitary-adrenal-axis. © Georg Thieme Verlag KG Stuttgart · New York.

  6. An autocrine ATP release mechanism regulates basal ciliary activity in airway epithelium.

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    Droguett, Karla; Rios, Mariana; Carreño, Daniela V; Navarrete, Camilo; Fuentes, Christian; Villalón, Manuel; Barrera, Nelson P

    2017-07-15

    antagonist used to block P2X7 receptors, which reduced basal CBF by 85%. Additionally, increasing extracellular ATP levels (0.1-100 μm) increased CBF, maintaining a sustained response that was suppressed in the presence of carbenoxolone. We also show that high levels of ATP (1 mm), associated with inflammatory conditions, lowered basal CBF by reducing [Ca 2+ ] i and hemichannel functionality. In summary, we provide evidence indicating that airway epithelium ATP release is the molecular autocrine mechanism regulating basal ciliary activity and is also the mediator of the ciliary response to chemical stimulation. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

  7. Activating basal-plane catalytic activity of two-dimensional MoS2 monolayer with remote hydrogen plasma

    KAUST Repository

    Cheng, Chia-Chin

    2016-09-10

    Two-dimensional layered transition metal dichalcogenide (TMD) materials such as Molybdenum disufide (MoS2) have been recognized as one of the low-cost and efficient electrocatalysts for hydrogen evolution reaction (HER). The crystal edges that account for a small percentage of the surface area, rather than the basal planes, of MoS2 monolayer have been confirmed as their active catalytic sites. As a result, extensive efforts have been developing in activating the basal planes of MoS2 for enhancing their HER activity. Here, we report a simple and efficient approach-using a remote hydrogen-plasma process-to creating S-vacancies on the basal plane of monolayer crystalline MoS2; this process can generate high density of S-vacancies while mainly maintaining the morphology and structure of MoS2 monolayer. The density of S-vacancies (defects) on MoS2 monolayers resulted from the remote hydrogen-plasma process can be tuned and play a critical role in HER, as evidenced in the results of our spectroscopic and electrical measurements. The H2-plasma treated MoS2 also provides an excellent platform for systematic and fundamental study of defect-property relationships in TMDs, which provides insights for future applications including electrical, optical and magnetic devices. © 2016 Elsevier Ltd.

  8. Activating basal-plane catalytic activity of two-dimensional MoS2 monolayer with remote hydrogen plasma

    KAUST Repository

    Cheng, Chia-Chin; Lu, Ang-Yu; Tseng, Chien-Chih; Yang, Xiulin; Hedhili, Mohamed N.; Chen, Min-Cheng; Wei, Kung-Hwa; Li, Lain-Jong

    2016-01-01

    that account for a small percentage of the surface area, rather than the basal planes, of MoS2 monolayer have been confirmed as their active catalytic sites. As a result, extensive efforts have been developing in activating the basal planes of MoS2

  9. Basal ganglia dysfunction in OCD: subthalamic neuronal activity correlates with symptoms severity and predicts high-frequency stimulation efficacy.

    Science.gov (United States)

    Welter, M-L; Burbaud, P; Fernandez-Vidal, S; Bardinet, E; Coste, J; Piallat, B; Borg, M; Besnard, S; Sauleau, P; Devaux, B; Pidoux, B; Chaynes, P; Tézenas du Montcel, S; Bastian, A; Langbour, N; Teillant, A; Haynes, W; Yelnik, J; Karachi, C; Mallet, L

    2011-05-03

    Functional and connectivity changes in corticostriatal systems have been reported in the brains of patients with obsessive-compulsive disorder (OCD); however, the relationship between basal ganglia activity and OCD severity has never been adequately established. We recently showed that deep brain stimulation of the subthalamic nucleus (STN), a central basal ganglia nucleus, improves OCD. Here, single-unit subthalamic neuronal activity was analysed in 12 OCD patients, in relation to the severity of obsessions and compulsions and response to STN stimulation, and compared with that obtained in 12 patients with Parkinson's disease (PD). STN neurons in OCD patients had lower discharge frequency than those in PD patients, with a similar proportion of burst-type activity (69 vs 67%). Oscillatory activity was present in 46 and 68% of neurons in OCD and PD patients, respectively, predominantly in the low-frequency band (1-8 Hz). In OCD patients, the bursty and oscillatory subthalamic neuronal activity was mainly located in the associative-limbic part. Both OCD severity and clinical improvement following STN stimulation were related to the STN neuronal activity. In patients with the most severe OCD, STN neurons exhibited bursts with shorter duration and interburst interval, but higher intraburst frequency, and more oscillations in the low-frequency bands. In patients with best clinical outcome with STN stimulation, STN neurons displayed higher mean discharge, burst and intraburst frequencies, and lower interburst interval. These findings are consistent with the hypothesis of a dysfunction in the associative-limbic subdivision of the basal ganglia circuitry in OCD's pathophysiology.

  10. EEG alpha rhythm, ocular activity and basal skin resistance

    NARCIS (Netherlands)

    Verbaten, M.N.; Beaujon, J.N.R.; Sjouw, W.

    Most hypotheses about the origin of the occipital alpha rhythm stress the specific influence of ocular activity. In this study, the influence of eye-movement frequency and extreme upward deviation of the eyeballs (enlarging the corneo-retinal potential) on occipital alpha activity and basal skin

  11. Treatment of basal cell epithelioma with high energy electron beam

    Energy Technology Data Exchange (ETDEWEB)

    Ogawa, Y. (Hyogo-ken Cancer Center, Kobe (Japan)); Kumano, M.; Kumano, K.

    1981-11-01

    Thirty patients with basal cell epithelioma received high energy electron beam therapy. They were irradiated with a dose ranging from 4,800 rad (24 fractions, 35 days) to 12,000 rad (40 fractions, 57 days). Tumors disappeared in all cases. These were no disease-related deaths; in one patient there was recurrence after 2 years. We conclude that radiotherapy with high energy electron beam is very effective in the treatment of basal cell epithelioma.

  12. Activity of the basal ganglia in Parkinson's disease estimated by PET

    International Nuclear Information System (INIS)

    Ohye, Chihiro

    1995-01-01

    Positron emission tomographic (PET) studies on the local cerebral blood flow, oxygen metabolic rate, glucose metabolic rate in the basal ganglia of Parkinson's disease are reviewed. PET has demonstrated that blood flow was decreased in the cerebral cortex, especially the frontal region, of Parkinson's disease and that specific change in blood flow or metabolic rate in the basal ganglia was detected only in patients with hemi-parkinsonism. In authors' study on PET using 18 FDG in patients with tremor type and rigid type Parkinson's disease, changes in blood flow and metabolic rate were minimal at the basal ganglia level in tremor type patients, but cortical blood flow was decreased and metabolic rate was more elevated in the basal ganglia in rigid type patients. These findings were correlated with depth micro-recordings obtained by stereotactic pallidotomy. PET studies have also revealed that activity in the nerve terminal was decreased with decreasing dopamine and that dopamine (mainly D 2 ) activity was remarkably increased. PET studies with specific tracers are promising in providing more accurate information about functional state of living human brain with minimal invasion to patients. (N.K.)

  13. Patterned basal seismicity shows sub-ice stream bedforms

    Science.gov (United States)

    Barcheck, C. G.; Tulaczyk, S. M.; Schwartz, S. Y.

    2017-12-01

    Patterns in seismicity emanating from the bottom of fast-moving ice streams and glaciers may indicate localized patches of higher basal resistance— sometimes called 'sticky spots', or otherwise varying basal properties. These seismogenic basal areas resist an unknown portion of the total driving stress of the Whillans Ice Plain (WIP), in West Antarctica, but may play an important role in the WIP stick-slip cycle and ice stream slowdown. To better understand the mechanism and importance of basal seismicity beneath the WIP, we analyze seismic data collected by a small aperture (micro-earthquakes in Dec 2014, and we compare the resulting map of seismicity to ice bottom depth measured by airborne radar. The number of basal earthquakes per area within the network is spatially heterogeneous, but a pattern of two 400m wide streaks of high seismicity rates is evident, with >50-500 earthquakes detected per 50x50m grid cell in 2 weeks. These seismically active streaks are elongated approximately in the ice flow direction with a spacing of 750m. Independent airborne radar measurements of ice bottom depth from Jan 2013 show a low-amplitude ( 5m) undulation in the basal topography superposed on a regional gradient in ice bottom depth. The flow-perpendicular wavelength of these low-amplitude undulations is comparable to the spacing of the high seismicity bands, and the streaks of high seismicity intersect local lows in the undulating basal topography. We interpret these seismic and radar observations as showing seismically active sub-ice stream bedforms that are low amplitude and elongated in the direction of ice flow, comparable to the morphology of mega scale glacial lineations (MSGLs), with high basal seismicity rates observed in the MSGL troughs. These results have implications for understanding the formation mechanism of MSGLS and well as understanding the interplay between basal topographic roughness, spatially varying basal till and hydrologic properties, basal

  14. Evaluation of basal sex hormone levels for activation of the hypothalamic-pituitary-gonadal axis.

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    Ding, Yu; Li, Juan; Yu, Yongguo; Yang, Peirong; Li, Huaiyuan; Shen, Yongnian; Huang, Xiaodong; Liu, Shijian

    2018-03-28

    This study aimed to identify the predictive value of basal sex hormone levels for activation of the hypothalamic-pituitary-gonadal (HPG) axis in girls. Gonadotropin-releasing hormone (GnRH) stimulation tests were performed and evaluated in a total of 1750 girls with development of secondary sex characteristics. Correlation analyses were conducted between basal sex hormones and peak luteinizing hormone (LH) levels ≥5 IU/L during the GnRH stimulation test. Receiver operating characteristic (ROC) curves for basal levels of LH, follicle-stimulating hormone (FSH), LH/FSH, and estradiol (E2) before the GnRH stimulation test were plotted. The area under the curve (AUC) and 95% confidence intervals (CIs) were measured for each curve. The maximum AUC value was observed for basal LH levels (0.77, 95% CI: 0.74-0.79), followed by basal FSH levels (0.73, 95% CI: 0.70-0.75), the basal LH/FSH ratio (0.68, 95% CI: 0.65-0.71), and basal E2 levels (0.61, 95% CI: 0.59-0.64). The appropriate cutoff value of basal LH levels associated with a positive response of the GnRH stimulation test was 0.35 IU/L, with a sensitivity of 63.96% and specificity of 76.3% from the ROC curves when Youden's index showed the maximum value. When 100% of patients had peak LH levels ≥5 IU/L, basal LH values were >2.72 IU/L, but the specificity was only 5.45%. Increased basal LH levels are a significant predictor of a positive response during the GnRH stimulation test for assessing activation of the HPG axis in most girls with early pubertal signs.

  15. Adenoid basal hyperplasia of the uterine cervix: a lesion of reserve cell type, distinct from adenoid basal carcinoma.

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    Kerdraon, Olivier; Cornélius, Aurélie; Farine, Marie-Odile; Boulanger, Loïc; Wacrenier, Agnès

    2012-12-01

    Adenoid basal hyperplasia is an underrecognized cervical lesion, resembling adenoid basal carcinoma, except the absence of deep invasion into the stroma. We report a series of 10 cases, all extending less than 1 mm from the basement membrane. Our results support the hypothesis that adenoid basal hyperplasia arises from reserve cells of the cervix. Lesions were found close to the squamocolumnar junction, in continuity with the nearby subcolumnar reserve cells. They shared the same morphology and immunoprofile using a panel of 4 antibodies (keratin 5/6, keratin 14, keratin 7 and p63) designed to differentiate reserve cells from mature squamous cells and endocervical columnar cells. We detected no human papillomavirus infection by in situ hybridization targeting high-risk human papillomavirus, which was concordant with the absence of immunohistochemical p16 expression. We demonstrated human papillomavirus infection in 4 (80%) of 5 adenoid basal carcinoma, which is in the same range as previous studies (88%). Thus, adenoid basal hyperplasia should be distinguished from adenoid basal carcinoma because they imply different risk of human papillomavirus infection and of subsequent association with high-grade invasive carcinoma. In our series, the most reliable morphological parameters to differentiate adenoid basal hyperplasia from adenoid basal carcinoma were the depth of the lesion and the size of the lesion nests. Furthermore, squamous differentiation was rare in adenoid basal hyperplasia and constant in adenoid basal carcinoma. Finally, any mitotic activity and/or an increase of Ki67 labeling index should raise the hypothesis of adenoid basal carcinoma. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Alterations in Neuronal Activity in Basal Ganglia-Thalamocortical Circuits in the Parkinsonian State

    Directory of Open Access Journals (Sweden)

    Adriana eGalvan

    2015-02-01

    Full Text Available In patients with Parkinson’s disease and in animal models of this disorder, neurons in the basal ganglia and related regions in thalamus and cortex show changes that can be recorded by using electrophysiologic single-cell recording techniques, including altered firing rates and patterns, pathologic oscillatory activity and increased inter-neuronal synchronization. In addition, changes in synaptic potentials or in the joint spiking activities of populations of neurons can be monitored as alterations in local field potentials, electroencephalograms or electrocorticograms. Most of the mentioned electrophysiologic changes are probably related to the degeneration of diencephalic dopaminergic neurons, leading to dopamine loss in the striatum and other basal ganglia nuclei, although degeneration of non-dopaminergic cell groups may also have a role. The altered electrical activity of the basal ganglia and associated nuclei may contribute to some of the motor signs of the disease. We here review the current knowledge of the electrophysiologic changes at the single cell level, the level of local populations of neural elements, and the level of the entire basal ganglia-thalamocortical network in parkinsonism, and discuss the possible use of this information to optimize treatment approaches to Parkinson’s disease, such as deep brain stimulation therapy.

  17. Alterations in neuronal activity in basal ganglia-thalamocortical circuits in the parkinsonian state

    Science.gov (United States)

    Galvan, Adriana; Devergnas, Annaelle; Wichmann, Thomas

    2015-01-01

    In patients with Parkinson’s disease and in animal models of this disorder, neurons in the basal ganglia and related regions in thalamus and cortex show changes that can be recorded by using electrophysiologic single-cell recording techniques, including altered firing rates and patterns, pathologic oscillatory activity and increased inter-neuronal synchronization. In addition, changes in synaptic potentials or in the joint spiking activities of populations of neurons can be monitored as alterations in local field potentials (LFPs), electroencephalograms (EEGs) or electrocorticograms (ECoGs). Most of the mentioned electrophysiologic changes are probably related to the degeneration of diencephalic dopaminergic neurons, leading to dopamine loss in the striatum and other basal ganglia nuclei, although degeneration of non-dopaminergic cell groups may also have a role. The altered electrical activity of the basal ganglia and associated nuclei may contribute to some of the motor signs of the disease. We here review the current knowledge of the electrophysiologic changes at the single cell level, the level of local populations of neural elements, and the level of the entire basal ganglia-thalamocortical network in parkinsonism, and discuss the possible use of this information to optimize treatment approaches to Parkinson’s disease, such as deep brain stimulation (DBS) therapy. PMID:25698937

  18. Modulating basal ganglia and cerebellar activity to suppress parkinsonian tremor

    NARCIS (Netherlands)

    Heida, Tjitske; Zhao, Yan; van Wezel, Richard Jack Anton

    2013-01-01

    Despite extensive research, the detailed pathophysiology of the parkinsonian tremor is still unknown. It has been hypothesized that the generation of parkinsonian tremor is related to abnormal activity within the basal ganglia. The cerebello-thalamic-cortical loop has been suggested to indirectly

  19. Effects of Electrical and Optogenetic Deep Brain Stimulation on Synchronized Oscillatory Activity in Parkinsonian Basal Ganglia.

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    Ratnadurai-Giridharan, Shivakeshavan; Cheung, Chung C; Rubchinsky, Leonid L

    2017-11-01

    Conventional deep brain stimulation of basal ganglia uses high-frequency regular electrical pulses to treat Parkinsonian motor symptoms but has a series of limitations. Relatively new and not yet clinically tested, optogenetic stimulation is an effective experimental stimulation technique to affect pathological network dynamics. We compared the effects of electrical and optogenetic stimulation of the basal gangliaon the pathologicalParkinsonian rhythmic neural activity. We studied the network response to electrical stimulation and excitatory and inhibitory optogenetic stimulations. Different stimulations exhibit different interactions with pathological activity in the network. We studied these interactions for different network and stimulation parameter values. Optogenetic stimulation was found to be more efficient than electrical stimulation in suppressing pathological rhythmicity. Our findings indicate that optogenetic control of neural synchrony may be more efficacious than electrical control because of the different ways of how stimulations interact with network dynamics.

  20. Activity of the rat osteocalcin basal promoter in osteoblastic cells is dependent upon homeodomain and CP1 binding motifs.

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    Towler, D A; Bennett, C D; Rodan, G A

    1994-05-01

    A detailed analysis of the transcriptional machinery responsible for osteoblast-specific gene expression should provide tools useful for understanding osteoblast commitment and differentiation. We have defined three cis-elements important for basal activity of the rat osteocalcin (OC) promoter, located at about -200 to -180, -170 to -138, and -121 to -64 relative to the transcription initiation site. A motif (TCTGATTGTGT) present in the region between -200 and -170 that binds a multisubunit CP1/NFY/CBF-like CAAT factor complex contributes significantly to high level basal activity and presumably functions as the CAAT box for the rat OC promoter. We show that the region -121 to 32 is sufficient to confer osteoblastic cell type specificity in transient transfection assays of cultured cell lines using luciferase as a reporter. The basal promoter is active in rodent osteoblastic cell lines, but not in rodent fibroblastic or muscle cell lines. Although the rat OC box (-100 to -74) contains a CAAT motif, we could not detect CP1-like CAAT factor binding to this region. In fact, we demonstrate that a Msx-1 (Hox 7.1) homeodomain binding motif (ACTAATTG; bottom strand) in the 3'-end of the rat OC box is necessary for high level activity of the rat OC basal promoter in osteoblastic cells. A nuclear factor that recognizes this motif appears to be present in osteoblastic ROS 17/2.8 cells, which produce OC, but not in fibroblastic ROS 25/1 cells, which fail to express OC. This ROS 17/2.8 nuclear factor also recognizes the A/T-rich DNA cognates of the homeodomain-containing POU family of transcription factors. Taken together, these data suggest that a ubiquitous CP1-like CAAT factor and a cell type-restricted homeodomain containing (Msx or POU family) transcription factor interact with the proximal rat OC promoter to direct appropriate basal OC transcription in osteoblastic cells.

  1. Endurance exercise training induces fat depot-specific differences in basal autophagic activity

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    Tanaka, Goki; Kato, Hisashi; Izawa, Tetsuya, E-mail: tizawa@mail.doshisha.ac.jp

    2015-10-23

    The purpose of this study was to uncover the effect of exercise training on the expression of autophagy marker proteins in epididymal white adipose tissue (eWAT), inguinal WAT (iWAT), and the stromal vascular fraction (SVF) collected from eWAT. Male Wistar rats aged 4–5 weeks were randomly divided into two groups, sedentary control (n = 7) and exercise-trained (n = 7). Rats in the exercise-trained group were exercised on a treadmill set at a 5° incline 5 days/week for 9 weeks. We determined that the expression levels of an autophagosome-associating form of microtubule-associated protein 1 light chain 3 (LC3)-II and of p62 were significantly higher in eWAT from exercise-trained than from control rats, while those of adipose-specific deletion of autophagy-related protein (ATG7) and lysosomal-associated membrane protein type 2A (LAMP2a) showed no difference between groups. However, in iWAT, the expression levels of LC3-II and ATG7 were significantly higher in exercise-trained than in control rats. The expression of p62 was highly correlated with that of peroxisome proliferator-activated receptor γ (PPARγ), a master regulator of adipogenesis and lipid metabolism, in both WAT types (eWAT, r = 0.856, P < 0.05; iWAT, r = 0.762, P < 0.05), whereas LC3-II and PPARγ levels were highly correlated in eWAT (r = 0.765, P < 0.05) but not in iWAT (r = −0.306, ns). In SVF, the expression levels of LC3II, ATG7, and LAMP2a were significantly higher in exercise-trained than in control rats. These results suggest that exercise training suppresses basal autophagy activity in eWAT, but that this activity is enhanced in iWAT and SVF collected from eWAT. Thus, the adaptation of basal autophagic activity following exercise training exhibits fat depot-specific differences. - Highlights: • Autophagy has been associated with obesity and associated diseases. • We examined exercise-associated rat white adipose tissue (WAT) autophagy markers. • Exercise increased

  2. Endurance exercise training induces fat depot-specific differences in basal autophagic activity

    International Nuclear Information System (INIS)

    Tanaka, Goki; Kato, Hisashi; Izawa, Tetsuya

    2015-01-01

    The purpose of this study was to uncover the effect of exercise training on the expression of autophagy marker proteins in epididymal white adipose tissue (eWAT), inguinal WAT (iWAT), and the stromal vascular fraction (SVF) collected from eWAT. Male Wistar rats aged 4–5 weeks were randomly divided into two groups, sedentary control (n = 7) and exercise-trained (n = 7). Rats in the exercise-trained group were exercised on a treadmill set at a 5° incline 5 days/week for 9 weeks. We determined that the expression levels of an autophagosome-associating form of microtubule-associated protein 1 light chain 3 (LC3)-II and of p62 were significantly higher in eWAT from exercise-trained than from control rats, while those of adipose-specific deletion of autophagy-related protein (ATG7) and lysosomal-associated membrane protein type 2A (LAMP2a) showed no difference between groups. However, in iWAT, the expression levels of LC3-II and ATG7 were significantly higher in exercise-trained than in control rats. The expression of p62 was highly correlated with that of peroxisome proliferator-activated receptor γ (PPARγ), a master regulator of adipogenesis and lipid metabolism, in both WAT types (eWAT, r = 0.856, P < 0.05; iWAT, r = 0.762, P < 0.05), whereas LC3-II and PPARγ levels were highly correlated in eWAT (r = 0.765, P < 0.05) but not in iWAT (r = −0.306, ns). In SVF, the expression levels of LC3II, ATG7, and LAMP2a were significantly higher in exercise-trained than in control rats. These results suggest that exercise training suppresses basal autophagy activity in eWAT, but that this activity is enhanced in iWAT and SVF collected from eWAT. Thus, the adaptation of basal autophagic activity following exercise training exhibits fat depot-specific differences. - Highlights: • Autophagy has been associated with obesity and associated diseases. • We examined exercise-associated rat white adipose tissue (WAT) autophagy markers. • Exercise increased

  3. Implications of basal micro-earthquakes and tremor for ice stream mechanics: Stick-slip basal sliding and till erosion

    Science.gov (United States)

    Barcheck, C. Grace; Tulaczyk, Slawek; Schwartz, Susan Y.; Walter, Jacob I.; Winberry, J. Paul

    2018-03-01

    The Whillans Ice Plain (WIP) is unique among Antarctic ice streams because it moves by stick-slip. The conditions allowing stick-slip and its importance in controlling ice dynamics remain uncertain. Local basal seismicity previously observed during unstable slip is a clue to the mechanism of ice stream stick-slip and a window into current basal conditions, but the spatial extent and importance of this basal seismicity are unknown. We analyze data from a 2010-2011 ice-plain-wide seismic and GPS network to show that basal micro-seismicity correlates with large-scale patterns in ice stream slip behavior: Basal seismicity is common where the ice moves the least between unstable slip events, with small discrete basal micro-earthquakes happening within 10s of km of the central stick-slip nucleation area and emergent basal tremor occurring downstream of this area. Basal seismicity is largely absent in surrounding areas, where inter-slip creep rates are high. The large seismically active area suggests that a frictional sliding law that can accommodate stick-slip may be appropriate for ice stream beds on regional scales. Variability in seismic behavior over inter-station distances of 1-10 km indicates heterogeneity in local bed conditions and frictional complexity. WIP unstable slips may nucleate when stick-slip basal earthquake patches fail over a large area. We present a conceptual model in which basal seismicity results from slip-weakening frictional failure of over-consolidated till as it is eroded and mobilized into deforming till.

  4. High basal Wnt signaling is further induced by PI3K/mTor inhibition but sensitive to cSRC inhibition in mammary carcinoma cell lines with HER2/3 overexpression

    International Nuclear Information System (INIS)

    Timmermans-Sprang, Elpetra P. M.; Gracanin, Ana; Mol, Jan A.

    2015-01-01

    Elevated basal, ligand-independent, Wnt signaling in some canine breast cancer cells is not caused by classical mutations in APC, β-Catenin or GSK3β but, at least partially, by enhanced LEF1 expression. We examined the expression and function of EGFR/HER-regulated pathways on the ligand-independent Wnt signaling. Twelve canine mammary tumor cell lines with previously reported differential basal Wnt activity were used. The expression levels of genes related to EGF-signaling were analyzed by cluster analysis. Cell lines with a combined overexpression of EGF-related genes and enhanced basal Wnt activity were treated with PI3K/mTor or cSRC inhibitors or transfected with a construct expressing wild-type PTEN. Subsequently, effects were measured on Wnt activity, cell proliferation, gene expression and protein level. High basal Wnt/LEF1 activity was associated with overexpression of HER2/3, ID1, ID2, RAC1 and HSP90 together with low to absent cMET and PTEN mRNA expression, suggesting a connection between Wnt- and HER-signaling pathways. Inhibition of the HER-regulated PI3K/mTor pathway using the dual PI3K/mTor inhibitor BEZ235 or the mTor inhibitor Everolimus® resulted in reduced cell proliferation. In the cell line with high basal Wnt activity, however, an unexpected further increased Wnt activity was found that could be greatly reduced after inhibition of the HER-regulated cSRC activity. Inhibition of the PI3K/mTor pathway was associated with enhanced expression of β-Catenin, Axin2, MUC1, cMET, EGFR and HER2 and a somewhat increased β-Catenin protein content, whereas cSRC inhibition was associated with slightly enhanced HER3 and SLUG mRNA expression. A high protein expression of HER3 was found only in a cell line with high basal Wnt activity. High basal Wnt activity in some mammary cancer cell lines is associated with overexpression of HER-receptor related genes and HER3 protein, and the absence of PTEN. Inhibition of the PI3K/mTor pathway further stimulated

  5. Basally activated nonselective cation currents regulate the resting membrane potential in human and monkey colonic smooth muscle

    Science.gov (United States)

    Dwyer, Laura; Rhee, Poong-Lyul; Lowe, Vanessa; Zheng, Haifeng; Peri, Lauren; Ro, Seungil; Sanders, Kenton M.

    2011-01-01

    Resting membrane potential (RMP) plays an important role in determining the basal excitability of gastrointestinal smooth muscle. The RMP in colonic muscles is significantly less negative than the equilibrium potential of K+, suggesting that it is regulated not only by K+ conductances but by inward conductances such as Na+ and/or Ca2+. We investigated the contribution of nonselective cation channels (NSCC) to the RMP in human and monkey colonic smooth muscle cells (SMC) using voltage- and current-clamp techniques. Qualitative reverse transcriptase-polymerase chain reaction was performed to examine potential molecular candidates for these channels among the transient receptor potential (TRP) channel superfamily. Spontaneous transient inward currents and holding currents were recorded in human and monkey SMC. Replacement of extracellular Na+ with equimolar tetraethylammonium or Ca2+ with Mn2+ inhibited basally activated nonselective cation currents. Trivalent cations inhibited these channels. Under current clamp, replacement of extracellular Na+ with N-methyl-d-glucamine or addition of trivalent cations caused hyperpolarization. Three unitary conductances of NSCC were observed in human and monkey colonic SMC. Molecular candidates for basally active NSCC were TRPC1, C3, C4, C7, M2, M4, M6, M7, V1, and V2 in human and monkey SMC. Comparison of the biophysical properties of these TRP channels with basally active NSCC (bINSCC) suggests that TRPM4 and specific TRPC heteromultimer combinations may underlie the three single-channel conductances of bINSCC. In conclusion, these findings suggest that basally activated NSCC contribute to the RMP in human and monkey colonic SMC and therefore may play an important role in determining basal excitability of colonic smooth muscle. PMID:21566016

  6. Elevated YAP and its downstream targets CCN1 and CCN2 in basal cell carcinoma: impact on keratinocyte proliferation and stromal cell activation.

    Science.gov (United States)

    Quan, Taihao; Xu, Yiru; Qin, Zhaoping; Robichaud, Patrick; Betcher, Stephanie; Calderone, Ken; He, Tianyuan; Johnson, Timothy M; Voorhees, John J; Fisher, Gary J

    2014-04-01

    Yes-associated protein (YAP) is a transcriptional co-activator of hippo signaling pathway, which plays an important role in organ size control and tumorigenesis. Here we report that YAP and its downstream transcriptional targets CCN1 and CCN2 are markedly elevated in keratinocytes in human skin basal cell carcinoma tumor islands. In human keratinocytes, knockdown of YAP significantly reduced expression of CCN1 and CCN2, and repressed proliferation and survival. This inhibition of proliferation and survival was rescued by restoration of CCN1 expression, but not by CCN2 expression. In basal cell carcinoma stroma, CCN2-regulated genes type I collagen, fibronectin, and α-smooth muscle actin were highly expressed. Furthermore, atomic force microscopy revealed increased tissue stiffness in basal cell carcinoma stroma compared to normal dermis. These data provide evidence that up-regulation of YAP in basal cell carcinoma impacts both aberrant keratinocyte proliferation, via CCN1, and tumor stroma cell activation and stroma remodeling, via CCN2. Targeting YAP and/or CCN1 and CCN2 may provide clinical benefit in basal cell carcinoma. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  7. Differences in cortical and pituitary activity in response to hypoglycaemia and cognitive testing in healthy men with different basal activity of the renin-angiotensin system

    DEFF Research Database (Denmark)

    Bie-Olsen, Lise G; Pedersen-Bjergaard, Ulrik; Kjaer, Troels W

    2010-01-01

    in cerebral activity during hypoglycaemia and cognitive testing in two groups of healthy men with different basal RAS activity. METHODS: Ten healthy men with high RAS activity and 10 with low activity underwent six oxygen-15-labelled water positron emission tomography scans: twice during normoglycaemia, twice......INTRODUCTION: High renin-angiotensin system (RAS) activity has been associated with a high risk of severe hypoglycaemia in patients with type 1 diabetes and with cognitive deterioration during experimental hypoglycaemia in healthy subjects. The aim of this study was to describe possible differences...... during insulin-induced hypoglycaemia and twice during post-hypoglycaemia. During the scans, the subjects performed a computer-based reaction time test. RESULTS: Occipital areas were consistently more activated in the low RAS group than in the high RAS group throughout all three conditions. During...

  8. In vivo characterization of high Basal signaling from the ghrelin receptor

    DEFF Research Database (Denmark)

    Petersen, Pia Steen; Woldbye, David P D; Madsen, Andreas Nygaard

    2009-01-01

    The receptor for the orexigenic peptide, ghrelin, is one of the most constitutively active 7TM receptors known, as demonstrated under in vitro conditions. Change in expression of a constitutively active receptor is associated with change in signaling independent of the endogenous ligand. In the f......The receptor for the orexigenic peptide, ghrelin, is one of the most constitutively active 7TM receptors known, as demonstrated under in vitro conditions. Change in expression of a constitutively active receptor is associated with change in signaling independent of the endogenous ligand....... In the following study, we found that the expression of the ghrelin receptor in the hypothalamus was up-regulated approximately 2-fold in rats both during 48-h fasting and by streptozotocin-induced hyperphagia. In a separate experiment, to probe for the effect of the high basal signaling of the ghrelin receptor...... in vivo, we used intracerebroventricular administration by osmotic pumps of a peptide [D-Arg(1), D-Phe(5), D-Trp(7,9), Leu(11)]-substance P. This peptide selectively displays inverse agonism at the ghrelin receptor as compared with an inactive control peptide with just a single amino acid substitution...

  9. Primary Cutaneous Carcinosarcoma of the Basal Cell Subtype Should Be Treated as a High-Risk Basal Cell Carcinoma.

    Science.gov (United States)

    Bourgeault, Emilie; Alain, Jimmy; Gagné, Eric

    2015-01-01

    Cutaneous carcinosarcoma is a rare primary tumor of the skin, characterized by biphasic epithelial and mesenchymal differentiation. Due to the limited number of cases reported, there is no consensus regarding treatment and prognosis. Some authors suggest that cutaneous carcinosarcomas should be viewed as aggressive tumors, with ancillary imaging used to evaluate potential metastatic disease. Other reports demonstrate an indolent disease course, especially with epidermal-type cutaneous carcinosarcomas. We report a case of cutaneous carcinosarcoma, which we treated with electrodessication and curettage following a shave biopsy. The tumor had an epithelial component resembling a basal cell carcinoma and a fibrosarcomatous stroma. At 1-year follow-up, our patient did not show evidence of recurrence or metastasis. Our case suggests that a cutaneous carcinosarcoma with an epithelial component composed of basal cell carcinoma can be regarded as a high-risk nonmelanoma skin cancer. © The Author(s) 2015.

  10. Oscillatory activity in the human basal ganglia: more than just beta, more than just Parkinson's disease.

    Science.gov (United States)

    Alegre, Manuel; Valencia, Miguel

    2013-10-01

    The implantation of deep brain stimulators in different structures of the basal ganglia to treat neurological and psychiatric diseases has allowed the recording of local field potential activity in these structures. The analysis of these signals has helped our understanding of basal ganglia physiology in health and disease. However, there remain some major challenges and questions for the future. In a recent work, Tan et al. (Tan, H., Pogosyan, A., Anam, A., Foltynie, T., Limousin, P., Zrinzo, L., et al. 2013. Frequency specific activity in subthalamic nucleus correlates with hand bradykinesia in Parkinson's disease. Exp. Neurol. 240,122-129) take profit of these recordings to study the changes in subthalamic oscillatory activity during the hold and release phases of a grasping paradigm, and correlate the changes in different frequency bands with performance parameters. They found that beta activity was related to the release phase, while force maintenance related most to theta and gamma/HFO activity. There was no significant effect of the motor state of the patient on this latter association. These findings suggest that the alterations in the oscillatory activity of the basal ganglia in Parkinson's disease are not limited to the beta band, and they involve aspects different from movement preparation and initiation. Additionally, these results highlight the usefulness of the combination of well-designed paradigms with recordings in off and on motor states (in Parkinson's disease), or in different pathologies, in order to understand not only the pathophysiology of the diseases affecting the patients, but also the normal physiology of the basal ganglia. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Ketamine-induced oscillations in the motor circuit of the rat basal ganglia.

    Directory of Open Access Journals (Sweden)

    María Jesús Nicolás

    Full Text Available Oscillatory activity can be widely recorded in the cortex and basal ganglia. This activity may play a role not only in the physiology of movement, perception and cognition, but also in the pathophysiology of psychiatric and neurological diseases like schizophrenia or Parkinson's disease. Ketamine administration has been shown to cause an increase in gamma activity in cortical and subcortical structures, and an increase in 150 Hz oscillations in the nucleus accumbens in healthy rats, together with hyperlocomotion.We recorded local field potentials from motor cortex, caudate-putamen (CPU, substantia nigra pars reticulata (SNr and subthalamic nucleus (STN in 20 awake rats before and after the administration of ketamine at three different subanesthetic doses (10, 25 and 50 mg/Kg, and saline as control condition. Motor behavior was semiautomatically quantified by custom-made software specifically developed for this setting.Ketamine induced coherent oscillations in low gamma (~ 50 Hz, high gamma (~ 80 Hz and high frequency (HFO, ~ 150 Hz bands, with different behavior in the four structures studied. While oscillatory activity at these three peaks was widespread across all structures, interactions showed a different pattern for each frequency band. Imaginary coherence at 150 Hz was maximum between motor cortex and the different basal ganglia nuclei, while low gamma coherence connected motor cortex with CPU and high gamma coherence was more constrained to the basal ganglia nuclei. Power at three bands correlated with the motor activity of the animal, but only coherence values in the HFO and high gamma range correlated with movement. Interactions in the low gamma band did not show a direct relationship to movement.These results suggest that the motor effects of ketamine administration may be primarily mediated by the induction of coherent widespread high-frequency activity in the motor circuit of the basal ganglia, together with a frequency

  12. Adenoid cystic carcinoma of the breast, high grade with basal phenotype, literature review

    Directory of Open Access Journals (Sweden)

    Enaam Junainah

    Full Text Available Adenoid cystic carcinoma (ACC is a rare type of breast carcinoma resembling adenoid cystic carcinoma of other sites. this type of tumors usually characterized by the exhibiting dual cell population of luminal and basaloid with specific growth pattern Most of these sub types are triple-negative with basal-like breast features (tumors that are devoid of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression, and express basal cell markers, they are usually low-grade but can be high grade, clinical behavior is indolent despite the nuclear grade, lymph node involvement or distant metastases which is rarely occur. Treatment is either simple mastectomy or lumpectomy. Chemotherapy, radiation and hormonal treatment have limited used in those cases. Keywords: Adenoid cystic carcinoma, Breast, Triple-negative and basal-like phenotype

  13. Effect of an 8-week practice of externally triggered speech on basal ganglia activity of stuttering and fluent speakers.

    Science.gov (United States)

    Toyomura, Akira; Fujii, Tetsunoshin; Kuriki, Shinya

    2015-04-01

    The neural mechanisms underlying stuttering are not well understood. It is known that stuttering appears when persons who stutter speak in a self-paced manner, but speech fluency is temporarily increased when they speak in unison with external trigger such as a metronome. This phenomenon is very similar to the behavioral improvement by external pacing in patients with Parkinson's disease. Recent imaging studies have also suggested that the basal ganglia are involved in the etiology of stuttering. In addition, previous studies have shown that the basal ganglia are involved in self-paced movement. Then, the present study focused on the basal ganglia and explored whether long-term speech-practice using external triggers can induce modification of the basal ganglia activity of stuttering speakers. Our study of functional magnetic resonance imaging revealed that stuttering speakers possessed significantly lower activity in the basal ganglia than fluent speakers before practice, especially when their speech was self-paced. After an 8-week speech practice of externally triggered speech using a metronome, the significant difference in activity between the two groups disappeared. The cerebellar vermis of stuttering speakers showed significantly decreased activity during the self-paced speech in the second compared to the first experiment. The speech fluency and naturalness of the stuttering speakers were also improved. These results suggest that stuttering is associated with defective motor control during self-paced speech, and that the basal ganglia and the cerebellum are involved in an improvement of speech fluency of stuttering by the use of external trigger. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Urokinase vs Tissue-Type Plasminogen Activator for Thrombolytic Evacuation of Spontaneous Intracerebral Hemorrhage in Basal Ganglia

    Directory of Open Access Journals (Sweden)

    Yuqian Li

    2017-08-01

    Full Text Available Spontaneous intracerebral hemorrhage (ICH is a devastating form of stroke, which leads to a high rate of mortality and poor neurological outcomes worldwide. Thrombolytic evacuation with urokinase-type plasminogen activator (uPA or tissue-type plasminogen activator (tPA has been showed to be a hopeful treatment for ICH. However, to the best of our knowledge, no clinical trials were reported to compare the efficacy and safety of these two fibrinolytics administrated following minimally invasive stereotactic puncture (MISP in patients with spontaneous basal ganglia ICH. Therefore, the authors intended here to evaluate the differential impact of uPA and tPA in a retrospective study. In the present study, a total of 86 patients with spontaneous ICH in basal ganglia using MISP received either uPA (uPA group, n = 45 or tPA (tPA group, n = 41, respectively. The clinical baseline characteristics prior to the operation were collected. In addition, therapeutic responses were assessed by the short-term outcomes within 30 days postoperation, as well as long-term outcomes at 1 year postoperation. Our findings showed that, in comparison with tPA, uPA was able to better promote hematoma evacuation and ameliorate perihematomal edema, but the differences were not statistically significant. Moreover, the long-term functional outcomes of both groups were similar, with no statistical difference. In conclusion, these results provide evidence supporting that uPA and tPA are similar in the efficacy and safety for thrombolytic evacuation in combination with MISP in patients with spontaneous basal ganglia ICH.

  15. Transgressive segregation for very low and high levels of basal resistance to powdery mildew in barley

    NARCIS (Netherlands)

    Aghnoum, R.; Niks, R.E.

    2011-01-01

    Basal resistance of barley to powdery mildew is a quantitatively inherited trait that limits the growth and sporulation of barley powdery mildew pathogen by a non-hypersensitive mechanism of defense. Two experimental barley lines were developed with a very high (ErBgh) and low (EsBgh) level of basal

  16. Auditory brainstem activity and development evoked by apical versus basal cochlear implant electrode stimulation in children.

    Science.gov (United States)

    Gordon, K A; Papsin, B C; Harrison, R V

    2007-08-01

    The role of apical versus basal cochlear implant electrode stimulation on central auditory development was examined. We hypothesized that, in children with early onset deafness, auditory development evoked by basal electrode stimulation would differ from that evoked more apically. Responses of the auditory nerve and brainstem, evoked by an apical and a basal implant electrode, were measured over the first year of cochlear implant use in 50 children with early onset severe to profound deafness who used hearing aids prior to implantation. Responses at initial stimulation were of larger amplitude and shorter latency when evoked by the apical electrode. No significant effects of residual hearing or age were found on initial response amplitudes or latencies. With implant use, responses evoked by both electrodes showed decreases in wave and interwave latencies reflecting decreased neural conduction time through the brainstem. Apical versus basal differences persisted with implant experience with one exception; eIII-eV interlatency differences decreased with implant use. Acute stimulation shows prolongation of basally versus apically evoked auditory nerve and brainstem responses in children with severe to profound deafness. Interwave latencies reflecting neural conduction along the caudal and rostral portions of the brainstem decreased over the first year of implant use. Differences in neural conduction times evoked by apical versus basal electrode stimulation persisted in the caudal but not rostral brainstem. Activity-dependent changes of the auditory brainstem occur in response to both apical and basal cochlear implant electrode stimulation.

  17. Endocytosis-independent function of clathrin heavy chain in the control of basal NF-κB activation.

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    Man Lyang Kim

    Full Text Available BACKGROUND: Nuclear factor-κB (NF-κB is a transcription factor that regulates the transcription of genes involved in a variety of biological processes, including innate and adaptive immunity, stress responses and cell proliferation. Constitutive or excessive NF-κB activity has been associated with inflammatory disorders and higher risk of cancer. In contrast to the mechanisms controlling inducible activation, the regulation of basal NF-κB activation is not well understood. Here we test whether clathrin heavy chain (CHC contributes to the regulation of basal NF-κB activity in epithelial cells. METHODOLOGY: Using RNA interference to reduce endogenous CHC expression, we found that CHC is required to prevent constitutive activation of NF-κB and gene expression. Immunofluorescence staining showed constitutive nuclear localization of the NF-κB subunit p65 in absence of stimulation after CHC knockdown. Elevated basal p65 nuclear localization is caused by constitutive phosphorylation and degradation of inhibitor of NF-κB alpha (IκBα through an IκB kinase α (IKKα-dependent mechanism. The role of CHC in NF-κB signaling is functionally relevant as constitutive expression of the proinflammatory chemokine interleukin-8 (IL-8, whose expression is regulated by NF-κB, was found after CHC knockdown. Disruption of clathrin-mediated endocytosis by chemical inhibition or depletion of the μ2-subunit of the endocytosis adaptor protein AP-2, and knockdown of clathrin light chain a (CHLa, failed to induce constitutive NF-κB activation and IL-8 expression, showing that CHC acts on NF-κB independently of endocytosis and CLCa. CONCLUSIONS: We conclude that CHC functions as a built-in molecular brake that ensures a tight control of basal NF-κB activation and gene expression in unstimulated cells. Furthermore, our data suggest a potential link between a defect in CHC expression and chronic inflammation disorder and cancer.

  18. Basal Ganglia Circuits as Targets for Neuromodulation in Parkinson Disease.

    Science.gov (United States)

    DeLong, Mahlon R; Wichmann, Thomas

    2015-11-01

    The revival of stereotactic surgery for Parkinson disease (PD) in the 1990s, with pallidotomy and then with high-frequency deep brain stimulation (DBS), has led to a renaissance in functional surgery for movement and other neuropsychiatric disorders. To examine the scientific foundations and rationale for the use of ablation and DBS for treatment of neurologic and psychiatric diseases, using PD as the primary example. A summary of the large body of relevant literature is presented on anatomy, physiology, pathophysiology, and functional surgery for PD and other basal ganglia disorders. The signs and symptoms of movement disorders appear to result largely from signature abnormalities in one of several parallel and largely segregated basal ganglia thalamocortical circuits (ie, the motor circuit). The available evidence suggests that the varied movement disorders resulting from dysfunction of this circuit result from propagated disruption of downstream network activity in the thalamus, cortex, and brainstem. Ablation and DBS act to free downstream networks to function more normally. The basal ganglia thalamocortical circuit may play a key role in the expression of disordered movement, and the basal ganglia-brainstem projections may play roles in akinesia and disturbances of gait. Efforts are under way to target circuit dysfunction in brain areas outside of the traditionally implicated basal ganglia thalamocortical system, in particular, the pedunculopontine nucleus, to address gait disorders that respond poorly to levodopa and conventional DBS targets. Deep brain stimulation is now the treatment of choice for many patients with advanced PD and other movement disorders. The success of DBS and other forms of neuromodulation for neuropsychiatric disorders is the result of the ability to modulate circuit activity in discrete functional domains within the basal ganglia circuitry with highly focused interventions, which spare uninvolved areas that are often disrupted with

  19. Imaging of basal cell carcinoma by high-definition optical coherence tomography

    DEFF Research Database (Denmark)

    Boone, M A L M; Norrenberg, S; Jemec, G B E

    2012-01-01

    With the continued development of noninvasive therapies for basal cell carcinoma (BCC) such as photodynamic therapy and immune therapies, noninvasive diagnosis and monitoring become increasingly relevant. High-definition optical coherence tomography (HD-OCT) is a high-resolution imaging tool, wit......, with micrometre resolution in both transversal and axial directions, enabling visualization of individual cells up to a depth of around 570 μm, and filling the imaging gap between conventional optical coherence tomography (OCT) and reflectance confocal microscopy (RCM)....

  20. The AAA protein spastin possesses two levels of basal ATPase activity.

    Science.gov (United States)

    Fan, Xiangyu; Lin, Zhijie; Fan, Guanghui; Lu, Jing; Hou, Yongfei; Habai, Gulijiazi; Sun, Linyue; Yu, Pengpeng; Shen, Yuequan; Wen, Maorong; Wang, Chunguang

    2018-04-30

    The AAA ATPase spastin is a microtubule-severing enzyme that plays important roles in various cellular events including axon regeneration. Herein, we found that the basal ATPase activity of spastin is negatively regulated by spastin concentration. By determining a spastin crystal structure, we demonstrate the necessity of intersubunit interactions between spastin AAA domains. Neutralization of the positive charges in the microtubule-binding domain (MTBD) of spastin dramatically decreases the ATPase activity at low concentration, although the ATP-hydrolyzing potential is not affected. These results demonstrate that, in addition to the AAA domain, the MTBD region of spastin is also involved in regulating ATPase activity, making interactions between spastin protomers more complicated than expected. © 2018 Federation of European Biochemical Societies.

  1. Basal ganglia neuronal activity during scanning eye movements in Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Tomáš Sieger

    Full Text Available The oculomotor role of the basal ganglia has been supported by extensive evidence, although their role in scanning eye movements is poorly understood. Nineteen Parkinsońs disease patients, which underwent implantation of deep brain stimulation electrodes, were investigated with simultaneous intraoperative microelectrode recordings and single channel electrooculography in a scanning eye movement task by viewing a series of colored pictures selected from the International Affective Picture System. Four patients additionally underwent a visually guided saccade task. Microelectrode recordings were analyzed selectively from the subthalamic nucleus, substantia nigra pars reticulata and from the globus pallidus by the WaveClus program which allowed for detection and sorting of individual neurons. The relationship between neuronal firing rate and eye movements was studied by crosscorrelation analysis. Out of 183 neurons that were detected, 130 were found in the subthalamic nucleus, 30 in the substantia nigra and 23 in the globus pallidus. Twenty percent of the neurons in each of these structures showed eye movement-related activity. Neurons related to scanning eye movements were mostly unrelated to the visually guided saccades. We conclude that a relatively large number of basal ganglia neurons are involved in eye motion control. Surprisingly, neurons related to scanning eye movements differed from neurons activated during saccades suggesting functional specialization and segregation of both systems for eye movement control.

  2. Basal ganglia neuronal activity during scanning eye movements in Parkinson's disease.

    Science.gov (United States)

    Sieger, Tomáš; Bonnet, Cecilia; Serranová, Tereza; Wild, Jiří; Novák, Daniel; Růžička, Filip; Urgošík, Dušan; Růžička, Evžen; Gaymard, Bertrand; Jech, Robert

    2013-01-01

    The oculomotor role of the basal ganglia has been supported by extensive evidence, although their role in scanning eye movements is poorly understood. Nineteen Parkinsońs disease patients, which underwent implantation of deep brain stimulation electrodes, were investigated with simultaneous intraoperative microelectrode recordings and single channel electrooculography in a scanning eye movement task by viewing a series of colored pictures selected from the International Affective Picture System. Four patients additionally underwent a visually guided saccade task. Microelectrode recordings were analyzed selectively from the subthalamic nucleus, substantia nigra pars reticulata and from the globus pallidus by the WaveClus program which allowed for detection and sorting of individual neurons. The relationship between neuronal firing rate and eye movements was studied by crosscorrelation analysis. Out of 183 neurons that were detected, 130 were found in the subthalamic nucleus, 30 in the substantia nigra and 23 in the globus pallidus. Twenty percent of the neurons in each of these structures showed eye movement-related activity. Neurons related to scanning eye movements were mostly unrelated to the visually guided saccades. We conclude that a relatively large number of basal ganglia neurons are involved in eye motion control. Surprisingly, neurons related to scanning eye movements differed from neurons activated during saccades suggesting functional specialization and segregation of both systems for eye movement control.

  3. T2-weighted high-intensity signals in the basal ganglia as an interesting image finding in Unverricht-Lundborg disease.

    Science.gov (United States)

    Korja, Miikka; Ferlazzo, Edoardo; Soilu-Hänninen, Merja; Magaudda, Adriana; Marttila, Reijo; Genton, Pierre; Parkkola, Riitta

    2010-01-01

    We conducted a search for white matter changes (WMCs) in 13 Unverricht-Lundborg disease patients and compared the prevalence of WMCs in these patients to age-matched long-term epileptics and healthy controls. ULD patients had significantly more T2-weighted high-intensity signals on MRI than control subjects, due to the increased prevalence of these signals in the basal ganglia. Interestingly, ULD patients with the basal ganglia changes were overweight. Basal ganglia T2-weighted high-intensity signals are novel findings in ULD. 2009 Elsevier B.V. All rights reserved.

  4. Prefrontal Activity and Connectivity with the Basal Ganglia during Performance of Complex Cognitive Tasks Is Associated with Apathy in Healthy Subjects.

    Science.gov (United States)

    Fazio, Leonardo; Logroscino, Giancarlo; Taurisano, Paolo; Amico, Graziella; Quarto, Tiziana; Antonucci, Linda Antonella; Barulli, Maria Rosaria; Mancini, Marina; Gelao, Barbara; Ferranti, Laura; Popolizio, Teresa; Bertolino, Alessandro; Blasi, Giuseppe

    2016-01-01

    Convergent evidence indicates that apathy affects cognitive behavior in different neurological and psychiatric conditions. Studies of clinical populations have also suggested the primary involvement of the prefrontal cortex and the basal ganglia in apathy. These brain regions are interconnected at both the structural and functional levels and are deeply involved in cognitive processes, such as working memory and attention. However, it is unclear how apathy modulates brain processing during cognition and whether such a modulation occurs in healthy young subjects. To address this issue, we investigated the link between apathy and prefrontal and basal ganglia function in healthy young individuals. We hypothesized that apathy may be related to sub-optimal activity and connectivity in these brain regions. Three hundred eleven healthy subjects completed an apathy assessment using the Starkstein's Apathy Scale and underwent fMRI during working memory and attentional performance tasks. Using an ROI approach, we investigated the association of apathy with activity and connectivity in the DLPFC and the basal ganglia. Apathy scores correlated positively with prefrontal activity and negatively with prefrontal-basal ganglia connectivity during both working memory and attention tasks. Furthermore, prefrontal activity was inversely related to attentional behavior. These results suggest that in healthy young subjects, apathy is a trait associated with inefficient cognitive-related prefrontal activity, i.e., it increases the need for prefrontal resources to process cognitive stimuli. Furthermore, apathy may alter the functional relationship between the prefrontal cortex and the basal ganglia during cognition.

  5. Prefrontal Activity and Connectivity with the Basal Ganglia during Performance of Complex Cognitive Tasks Is Associated with Apathy in Healthy Subjects.

    Directory of Open Access Journals (Sweden)

    Leonardo Fazio

    Full Text Available Convergent evidence indicates that apathy affects cognitive behavior in different neurological and psychiatric conditions. Studies of clinical populations have also suggested the primary involvement of the prefrontal cortex and the basal ganglia in apathy. These brain regions are interconnected at both the structural and functional levels and are deeply involved in cognitive processes, such as working memory and attention. However, it is unclear how apathy modulates brain processing during cognition and whether such a modulation occurs in healthy young subjects. To address this issue, we investigated the link between apathy and prefrontal and basal ganglia function in healthy young individuals. We hypothesized that apathy may be related to sub-optimal activity and connectivity in these brain regions.Three hundred eleven healthy subjects completed an apathy assessment using the Starkstein's Apathy Scale and underwent fMRI during working memory and attentional performance tasks. Using an ROI approach, we investigated the association of apathy with activity and connectivity in the DLPFC and the basal ganglia.Apathy scores correlated positively with prefrontal activity and negatively with prefrontal-basal ganglia connectivity during both working memory and attention tasks. Furthermore, prefrontal activity was inversely related to attentional behavior.These results suggest that in healthy young subjects, apathy is a trait associated with inefficient cognitive-related prefrontal activity, i.e., it increases the need for prefrontal resources to process cognitive stimuli. Furthermore, apathy may alter the functional relationship between the prefrontal cortex and the basal ganglia during cognition.

  6. High signal intensity lesion in basal ganglia on MR imaging: correlation with portal-systemic encephalopathy in liver cirrhosis

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yun Ju; Choi, Sun Jeong; Kim, Chang Soo; Kim, Sun Hee; Chung, Chun Phil; Kim, Yang Sook [Maryknoll Hospital, Pusan (Korea, Republic of)

    1993-01-15

    To evaluate of the relationship between basal ganglia lesion and portal-systemic encephalopathy, eleven patients who had clinically proved liver cirrhosis with superior mesenteric vein larger than 10mm in diameter on ultrasonogram underwent brain MR imaging. No evidence of clinical or neuropsychiatric disturbance was observed in any patient at the time of the MR examination. Brain MR imaging revealed basal ganglia lesion characterized by bilateral, symmetric, high signal intensity without edema or mass effect on spin echo T1-weighted images in nine patients which included three patients with the past history of portal-systemic encephalopathy. It was concluded that excepted in the circumstances of other causes of the high signal intensity in basal ganglia on T1-weighted images such as fat, methemoglobin, melanin, neurofibromatosis, dense calcification, and parenteral nutrition, bilateral and symmetric high signal intensity lesion in basal ganglia would be a useful MR finding of subclinical portal-systemic encephalopathy in liver cirrhosis patients with no clinical or neuropsychiatric symptoms and larger than 10mm in diameter of superior mesenteric vein in ultrasonography.

  7. High signal intensity lesion in basal ganglia on MR imaging: correlation with portal-systemic encephalopathy in liver cirrhosis

    International Nuclear Information System (INIS)

    Kim, Yun Ju; Choi, Sun Jeong; Kim, Chang Soo; Kim, Sun Hee; Chung, Chun Phil; Kim, Yang Sook

    1993-01-01

    To evaluate of the relationship between basal ganglia lesion and portal-systemic encephalopathy, eleven patients who had clinically proved liver cirrhosis with superior mesenteric vein larger than 10mm in diameter on ultrasonogram underwent brain MR imaging. No evidence of clinical or neuropsychiatric disturbance was observed in any patient at the time of the MR examination. Brain MR imaging revealed basal ganglia lesion characterized by bilateral, symmetric, high signal intensity without edema or mass effect on spin echo T1-weighted images in nine patients which included three patients with the past history of portal-systemic encephalopathy. It was concluded that excepted in the circumstances of other causes of the high signal intensity in basal ganglia on T1-weighted images such as fat, methemoglobin, melanin, neurofibromatosis, dense calcification, and parenteral nutrition, bilateral and symmetric high signal intensity lesion in basal ganglia would be a useful MR finding of subclinical portal-systemic encephalopathy in liver cirrhosis patients with no clinical or neuropsychiatric symptoms and larger than 10mm in diameter of superior mesenteric vein in ultrasonography

  8. High frequency stimulation of the entopeduncular nucleus sets the cortico-basal ganglia network to a new functional state in the dystonic hamster.

    Science.gov (United States)

    Reese, René; Charron, Giselle; Nadjar, Agnès; Aubert, Incarnation; Thiolat, Marie-Laure; Hamann, Melanie; Richter, Angelika; Bezard, Erwan; Meissner, Wassilios G

    2009-09-01

    High frequency stimulation (HFS) of the internal pallidum is effective for the treatment of dystonia. Only few studies have investigated the effects of stimulation on the activity of the cortex-basal ganglia network. We here assess within this network the effect of entopeduncular nucleus (EP) HFS on the expression of c-Fos and cytochrome oxidase subunit I (COI) in the dt(sz)-hamster, a well-characterized model of paroxysmal dystonia. In dt(sz)-hamsters, we identified abnormal activity in motor cortex, basal ganglia and thalamus. These structures have already been linked to the pathophysiology of human dystonia. EP-HFS (i) increased striatal c-Fos expression in controls and dystonic hamsters and (ii) reduced thalamic c-Fos expression in dt(sz)-hamsters. EP-HFS had no effect on COI expression. The present results suggest that EP-HFS induces a new network activity state which may improve information processing and finally reduces the severity of dystonic attacks in dt(sz)-hamsters.

  9. The basal kinetic parameters of glycogen synthase in human myotube cultures are not affected by chronic high insulin exposure

    DEFF Research Database (Denmark)

    Gaster, M; Schrøder, H D; Handberg, A

    2001-01-01

    results show that chronic exposure of human myotubes to high insulin with or without high glucose did not affect the basal kinetic parameters but abolished the reactivity of GS to acute insulin stimulation. We suggest that insulin induced insulin resistance of GS is caused by a failure of acute insulin......There is no consensus regarding the results from in vivo and in vitro studies on the impact of chronic high insulin and/or high glucose exposure on acute insulin stimulation of glycogen synthase (GS) kinetic parameters in human skeletal muscle. The aim of this study was to evaluate the kinetic...... parameters of glycogen synthase activity in human myotube cultures at conditions of chronic high insulin combined or not with high glucose exposure, before and after a subsequent acute insulin stimulation. Acute insulin stimulation significantly increased the fractional activity (FV(0.1)) of GS, increased...

  10. Inverting adherent cells for visualizing ECM interactions at the basal cell side

    Energy Technology Data Exchange (ETDEWEB)

    Gudzenko, Tetyana [DFG-Center for Functional Nanostructures, Karlsruhe Institute of Technology (KIT), Wolfgang-Gaede-Strasse 1a, 76131 Karlsruhe (Germany); Franz, Clemens M., E-mail: clemens.franz@kit.edu [DFG-Center for Functional Nanostructures, Karlsruhe Institute of Technology (KIT), Wolfgang-Gaede-Strasse 1a, 76131 Karlsruhe (Germany)

    2013-05-15

    Interactions with the extracellular matrix (ECM) govern a wide range of cellular functions, including survival, migration and invasion. However, in adherent cells these interactions occur primarily on the basal cell side, making them inaccessible to high-resolution, surface-scanning imaging techniques such as atomic force microscopy (AFM) or scanning electron microscopy (SEM). Here we describe a fast and reliable method for inverting adherent cells, exposing the basal cell membrane for direct analysis by AFM or SEM in combination with fluorescence microscopy. Cells including their matrix adhesion sites remain intact during the inversion process and are transferred together with the complete array of basally associated ECM proteins. Molecular features of ECM proteins, such as the characteristic 67 nm collagen D-periodicity, are well preserved after inversion. To demonstrate the versatility of the method, we compared basal interactions of fibroblasts with fibrillar collagen I and fibronectin matrices. While fibroblasts remodel the fibronectin layer exclusively from above, they actively invade even thin collagen layers by contacting individual collagen nanofibrils both basally and apically through a network of cellular extensions. Cell–matrix entanglement coincides with enhanced cell spreading and flattening, indicating that nanoscale ECM interactions govern macroscopic changes in cell morphology. The presented cell inversion technique can thus provide novel insight into nanoscale cell–matrix interactions at the basal cell side. - Highlights: ► We present a novel method for inverting adherent cells to expose the basal cell side. ► Basal cell sides can be imaged at high resolution by AFM and SEM. ► Cells can be inverted together with the underlying extracellular matrix. ► AFM images of inverted cells provide a nanoscale look at basal cell–ECM interactions.

  11. Basal Cell Carcinoma

    Science.gov (United States)

    ... Kids’ zone Video library Find a dermatologist Basal cell carcinoma Overview Basal cell carcinoma: This skin cancer ... that has received years of sun exposure. Basal cell carcinoma: Overview Basal cell carcinoma (BCC) is the ...

  12. Deep Brain Stimulation for Movement Disorders of Basal Ganglia Origin: Restoring Function or Functionality?

    Science.gov (United States)

    Wichmann, Thomas; DeLong, Mahlon R

    2016-04-01

    Deep brain stimulation (DBS) is highly effective for both hypo- and hyperkinetic movement disorders of basal ganglia origin. The clinical use of DBS is, in part, empiric, based on the experience with prior surgical ablative therapies for these disorders, and, in part, driven by scientific discoveries made decades ago. In this review, we consider anatomical and functional concepts of the basal ganglia relevant to our understanding of DBS mechanisms, as well as our current understanding of the pathophysiology of two of the most commonly DBS-treated conditions, Parkinson's disease and dystonia. Finally, we discuss the proposed mechanism(s) of action of DBS in restoring function in patients with movement disorders. The signs and symptoms of the various disorders appear to result from signature disordered activity in the basal ganglia output, which disrupts the activity in thalamocortical and brainstem networks. The available evidence suggests that the effects of DBS are strongly dependent on targeting sensorimotor portions of specific nodes of the basal ganglia-thalamocortical motor circuit, that is, the subthalamic nucleus and the internal segment of the globus pallidus. There is little evidence to suggest that DBS in patients with movement disorders restores normal basal ganglia functions (e.g., their role in movement or reinforcement learning). Instead, it appears that high-frequency DBS replaces the abnormal basal ganglia output with a more tolerable pattern, which helps to restore the functionality of downstream networks.

  13. [Soil basal respiration and enzyme activities in the root-layer soil of tea bushes in a red soil].

    Science.gov (United States)

    Yu, Shen; He, Zhenli; Zhang, Rongguang; Chen, Guochao; Huang, Changyong

    2003-02-01

    Soil basal respiration potential, metabolic quotient (qCO2), and activities of urease, invertase and acid phosphomonoesterase were investigated in the root-layer of 10-, 40-, and 90-yr-old tea bushes grown on the same type of red soil. The soil daily basal respiration potential ranged from 36.23 to 58.52 mg.kg-1.d-1, and the potentials in the root-layer of 40- or 90-yr-old were greater than that of 10-yr old tea bushes. The daily qCO2, ranging from 0.30 to 0.68, was in the reverse trend. The activities of test three enzymes changed differently with tea bushes' age. Urease activity in the root-layer of all age tea bushes ranged from 41.48 to 47.72 mg.kg-1.h-1 and slightly decreased with tea bushes' age. Invertase activity was 189.29-363.40 mg.kg-1.h-1 and decreased with tea bushes' age, but its activity in the root-layer of 10-year old tea bushes was significantly greater than that in the root-layer soil of 40- or 90-year old tea bushes. Acid phosphomonoesterase activity (444.22-828.32 mg.kg-1.h-1) increased significantly with tea bushes' age. Soil basal respiration potential, qCO2 and activities of 3 soil enzymes were closely related to soil pH, soil organic carbon, total nitrogen and C/N ratio, total soluble phenol, and microbial biomass carbon, respectively.

  14. Basal ganglia and cortical networks for sequential ordering and rhythm of complex movements

    Directory of Open Access Journals (Sweden)

    Jeffery G. Bednark

    2015-07-01

    Full Text Available Voluntary actions require the concurrent engagement and coordinated control of complex temporal (e.g. rhythm and ordinal motor processes. Using high-resolution functional magnetic resonance imaging (fMRI and multi-voxel pattern analysis (MVPA, we sought to determine the degree to which these complex motor processes are dissociable in basal ganglia and cortical networks. We employed three different finger-tapping tasks that differed in the demand on the sequential temporal rhythm or sequential ordering of submovements. Our results demonstrate that sequential rhythm and sequential order tasks were partially dissociable based on activation differences. The sequential rhythm task activated a widespread network centered around the SMA and basal-ganglia regions including the dorsomedial putamen and caudate nucleus, while the sequential order task preferentially activated a fronto-parietal network. There was also extensive overlap between sequential rhythm and sequential order tasks, with both tasks commonly activating bilateral premotor, supplementary motor, and superior/inferior parietal cortical regions, as well as regions of the caudate/putamen of the basal ganglia and the ventro-lateral thalamus. Importantly, within the cortical regions that were active for both complex movements, MVPA could accurately classify different patterns of activation for the sequential rhythm and sequential order tasks. In the basal ganglia, however, overlapping activation for the sequential rhythm and sequential order tasks, which was found in classic motor circuits of the putamen and ventro-lateral thalamus, could not be accurately differentiated by MVPA. Overall, our results highlight the convergent architecture of the motor system, where complex motor information that is spatially distributed in the cortex converges into a more compact representation in the basal ganglia.

  15. Basal ganglia circuits changes in Parkinson's disease patients.

    Science.gov (United States)

    Wu, Tao; Wang, Jue; Wang, Chaodong; Hallett, Mark; Zang, Yufeng; Wu, Xiaoli; Chan, Piu

    2012-08-22

    Functional changes in basal ganglia circuitry are responsible for the major clinical features of Parkinson's disease (PD). Current models of basal ganglia circuitry can only partially explain the cardinal symptoms in PD. We used functional MRI to investigate the causal connectivity of basal ganglia networks from the substantia nigra pars compacta (SNc) in PD in the movement and resting state. In controls, SNc activity predicted increased activity in the supplementary motor area, the default mode network, and dorsolateral prefrontal cortex, but, in patients, activity predicted decreases in the same structures. The SNc had decreased connectivity with the striatum, globus pallidus, subthalamic nucleus, thalamus, supplementary motor area, dorsolateral prefrontal cortex, insula, default mode network, temporal lobe, cerebellum, and pons in patients compared to controls. Levodopa administration partially normalized the pattern of connectivity. Our findings show how the dopaminergic system exerts influences on widespread brain networks, including motor and cognitive networks. The pattern of basal ganglia network connectivity is abnormal in PD secondary to dopamine depletion, and is more deviant in more severe disease. Use of functional MRI with network analysis appears to be a useful method to demonstrate basal ganglia pathways in vivo in human subjects. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  16. Effect of diet with omega-3 in basal brain electrical activity and during status epilepticus in rats.

    Science.gov (United States)

    Pessoa, Daniella Tavares; da Silva, Eva Luana Almeida; Costa, Edbhergue Ventura Lola; Nogueira, Romildo Albuquerque

    2017-11-01

    Western diets are high in saturated fat and low in omega-3. Certain animals cannot produce omega-3 from their own lipids, making it necessary for it to be acquired from the diet. However, omega-3s are important components of the plasma membrane, and altering their proportions can promote physical and chemical alterations in the membranes, which may modify neuronal excitability. These alterations occur in healthy individuals, as well as in patients with epilepsy who are more sensitive to changes in brain electrical activity. This study evaluated the effect of a diet supplemented with omega-3 on the basal brain electrical activity both before and during status epilepticus in rats. To evaluate the brain electrical activity, we recorded electrocorticograms (ECoG) of animals both with and without omega-3 supplementation before and during status epilepticus induced by pilocarpine. Calculation of the average brain wave power by a power spectrum revealed that omega-3 supplementation reduced the average power of the delta wave by 20% and increased the average power of the beta wave by 45%. These effects were exacerbated when status epilepticus was induced in the animals supplemented with omega-3. The animals with and without omega-3 supplementation exhibited increases in basal brain electrical activities during status epilepticus. The two groups showed hyperactivity, but no significant difference between them was noted. Even though the brain activity levels observed during status epilepticus were similar between the two groups, neuron damage to the animals supplemented with omega-3 was more slight, revealing the neuroprotective effect of the omega-3. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. What basal ganglia changes underlie the parkinsonian state? The significance of neuronal oscillatory activity

    Science.gov (United States)

    Quiroga-Varela, A.; Walters, J.R.; Brazhnik, E.; Marin, C.; Obeso, J.A.

    2014-01-01

    One well accepted functional feature of the parkinsonian state is the recording of enhanced beta oscillatory activity in the basal ganglia. This has been demonstrated in patients with Parkinson's disease (PD) and in animal models such as the rat with 6-hydroxydopamine (6-OHDA)-induced lesion and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys, all of which are associated with severe striatal dopamine depletion. Neuronal hyper-synchronization in the beta (or any other) band is not present despite the presence of bradykinetic features in the rat and monkey models, suggesting that increased beta band power may arise when nigro-striatal lesion is advanced and that it is not an essential feature of the early parkinsonian state. Similar observations and conclusions have been previously made for increased neuronal firing rate in the subthalamic and globus pallidus pars interna nuclei. Accordingly, it is suggested that early parkinsonism may be associated with dynamic changes in basal ganglia output activity leading to reduced movement facilitation that may be an earlier feature of the parkinsonian state. PMID:23727447

  18. Fusarium basal rot in the Netherlands

    NARCIS (Netherlands)

    Visser, de C.L.M.; Broek, van den R.C.F.M.; Brink, van den L.

    2006-01-01

    Fusarium basal rot of onion, caused by Fusarium oxysporum f.sp. cepae, is a steadily increasing problem in The Netherlands. Financial losses for Dutch farmers confronted with Fusarium basal rot is substantial, due to yield reduction and high storage costs. This paper describes the development and

  19. Frequency and function in the basal ganglia: the origins of beta and gamma band activity.

    Science.gov (United States)

    Blenkinsop, Alexander; Anderson, Sean; Gurney, Kevin

    2017-07-01

    Neuronal oscillations in the basal ganglia have been observed to correlate with behaviours, although the causal mechanisms and functional significance of these oscillations remain unknown. We present a novel computational model of the healthy basal ganglia, constrained by single unit recordings from non-human primates. When the model is run using inputs that might be expected during performance of a motor task, the network shows emergent phenomena: it functions as a selection mechanism and shows spectral properties that match those seen in vivo. Beta frequency oscillations are shown to require pallido-striatal feedback, and occur with behaviourally relevant cortical input. Gamma oscillations arise in the subthalamic-globus pallidus feedback loop, and occur during movement. The model provides a coherent framework for the study of spectral, temporal and functional analyses of the basal ganglia and lays the foundation for an integrated approach to study basal ganglia pathologies such as Parkinson's disease in silico. Neural oscillations in the basal ganglia (BG) are well studied yet remain poorly understood. Behavioural correlates of spectral activity are well described, yet a quantitative hypothesis linking time domain dynamics and spectral properties to BG function has been lacking. We show, for the first time, that a unified description is possible by interpreting previously ignored structure in data describing globus pallidus interna responses to cortical stimulation. These data were used to expose a pair of distinctive neuronal responses to the stimulation. This observation formed the basis for a new mathematical model of the BG, quantitatively fitted to the data, which describes the dynamics in the data, and is validated against other stimulus protocol experiments. A key new result is that when the model is run using inputs hypothesised to occur during the performance of a motor task, beta and gamma frequency oscillations emerge naturally during static-force and

  20. Nevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome).

    Science.gov (United States)

    Bresler, Scott C; Padwa, Bonnie L; Granter, Scott R

    2016-06-01

    Nevoid basal cell carcinoma syndrome, or basal cell nevus syndrome (Gorlin syndrome), is a rare autosomal dominantly inherited disorder that is characterized by development of basal cell carcinomas from a young age. Other distinguishing clinical features are seen in a majority of patients, and include keratocystic odontogenic tumors (formerly odontogenic keratocysts) as well as dyskeratotic palmar and plantar pitting. A range of skeletal and other developmental abnormalities are also often seen. The disorder is caused by defects in hedgehog signaling which result in constitutive pathway activity and tumor cell proliferation. As sporadic basal cell carcinomas also commonly harbor hedgehog pathway aberrations, therapeutic agents targeting key signaling constituents have been developed and tested against advanced sporadically occurring tumors or syndromic disease, leading in 2013 to FDA approval of the first hedgehog pathway-targeted small molecule, vismodegib. The elucidation of the molecular pathogenesis of nevoid basal cell carcinoma syndrome has resulted in further understanding of the most common human malignancy.

  1. Dynamic stereotypic responses of basal ganglia neurons to subthalamic nucleus high frequency stimulation in the parkinsonian primate

    Directory of Open Access Journals (Sweden)

    Anan eMoran

    2011-04-01

    Full Text Available Deep brain stimulation in the subthalamic nucleus (STN is a well-established therapy for patients with severe Parkinson‟s disease (PD; however, its mechanism of action is still unclear. In this study we explored static and dynamic activation patterns in the basal ganglia during high frequency macro-stimulation of the STN. Extracellular multi-electrode recordings were performed in primates rendered parkinsonian using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Recordings were preformed simultaneously in the STN and the globus pallidus externus and internus. Single units were recorded preceding and during the stimulation. During the stimulation, STN mean firing rate dropped significantly, while pallidal mean firing rates did not change significantly. The vast majority of neurons across all three nuclei displayed stimulation driven modulations, which were stereotypic within each nucleus but differed across nuclei. The predominant response pattern of STN neurons was somatic inhibition. However, most pallidal neurons demonstrated synaptic activation patterns. A minority of neurons across all nuclei displayed axonal activation. Temporal dynamics were observed in the response to stimulation over the first 10 seconds in the STN and over the first 30 seconds in the pallidum. In both pallidal segments, the synaptic activation response patterns underwent delay and decay of the magnitude of the peak response due to short term synaptic depression. We suggest that during STN macro stimulation the STN goes through a functional ablation as its upper bound on information transmission drops significantly. This notion is further supported by the evident dissociation between the stimulation driven pre-synaptic STN somatic inhibition and the post-synaptic axonal activation of its downstream targets. Thus, basal ganglia output maintains its firing rate while losing the deleterious effect of the STN. This may be a part of the mechanism leading to the beneficial

  2. Basal metabolic regulatory responses and rhythmic activity of ...

    African Journals Online (AJOL)

    ... Rattus sp. Low concentrations of kola nut extract stimulated the heart by increasing rate and force of contraction as well as metabolic rate. Higher concentrations reduced rate and amplitude of beat resulting, at still higher concentrations in heart failure. Keywords: Kolanut, extract, basal metabolic rate, mammalian heart ...

  3. The Pedunculopontine Tegmental Nucleus as a Motor and Cognitive Interface between the Cerebellum and Basal Ganglia.

    Science.gov (United States)

    Mori, Fumika; Okada, Ken-Ichi; Nomura, Taishin; Kobayashi, Yasushi

    2016-01-01

    As an important component of ascending activating systems, brainstem cholinergic neurons in the pedunculopontine tegmental nucleus (PPTg) are involved in the regulation of motor control (locomotion, posture and gaze) and cognitive processes (attention, learning and memory). The PPTg is highly interconnected with several regions of the basal ganglia, and one of its key functions is to regulate and relay activity from the basal ganglia. Together, they have been implicated in the motor control system (such as voluntary movement initiation or inhibition), and modulate aspects of executive function (such as motivation). In addition to its intimate connection with the basal ganglia, projections from the PPTg to the cerebellum have been recently reported to synaptically activate the deep cerebellar nuclei. Classically, the cerebellum and basal ganglia were regarded as forming separated anatomical loops that play a distinct functional role in motor and cognitive behavioral control. Here, we suggest that the PPTg may also act as an interface device between the basal ganglia and cerebellum. As such, part of the therapeutic effect of PPTg deep brain stimulation (DBS) to relieve gait freezing and postural instability in advanced Parkinson's disease (PD) patients might also involve modulation of the cerebellum. We review the anatomical position and role of the PPTg in the pathway of basal ganglia and cerebellum in relation to motor control, cognitive function and PD.

  4. The pedunculopontine tegmental nucleus as a motor and cognitive interface between the cerebellum and basal ganglia

    Directory of Open Access Journals (Sweden)

    Fumika Mori

    2016-11-01

    Full Text Available As an important component of ascending activating systems, brainstem cholinergic neurons in the pedunculopontine tegmental nucleus (PPTg are involved in the regulation of motor control (locomotion, posture and gaze and cognitive processes (attention, learning, and memory. The PPTg is highly interconnected with several regions of the basal ganglia, and one of its key functions is to regulate and relay activity from the basal ganglia. Together, they have been implicated in the motor control system (such as voluntary movement initiation or inhibition, and modulate aspects of executive function (such as motivation. In addition to its intimate connection with the basal ganglia, projections from the PPTg to the cerebellum have been recently reported to synaptically activate the deep cerebellar nuclei. Classically, the cerebellum and basal ganglia were regarded as forming separated anatomical loops that play a distinct functional role in motor and cognitive behavioral control. Here, we suggest that the PPTg may also act as an interface device between the basal ganglia and cerebellum. As such, part of the therapeutic effect of PPTg deep brain stimulation to relieve gait freezing and postural instability in advanced Parkinson’s disease patients might also involve modulation of the cerebellum. We review the anatomical position and role of the PPTg in the pathway of basal ganglia and cerebellum in relation to motor control, cognitive function, and Parkinson’s disease.

  5. Complex Dynamics in the Basal Ganglia: Health and Disease Beyond the Motor System.

    Science.gov (United States)

    Andres, Daniela S; Darbin, Olivier

    2018-01-01

    The rate and oscillatory hypotheses are the two main current frameworks of basal ganglia pathophysiology. Both hypotheses have emerged from research on movement disorders sharing similar conceptualizations. These pathological conditions are classified either as hypokinetic or hyperkinetic, and the electrophysiological hallmarks of basal ganglia dysfunction are categorized as prokinetic or antikinetic. Although nonmotor symptoms, including neurobehavioral symptoms, are a key manifestation of basal ganglia dysfunction, they are uncommonly accounted for in these models. In patients with Parkinson's disease, the broad spectrum of motor symptoms and neurobehavioral symptoms challenges the concept that basal ganglia disorders can be classified into two categories. The profile of symptoms of basal ganglia dysfunction is best characterized by a breakdown of information processing, accompanied at an electrophysiological level by complex alterations of spiking activity from basal ganglia neurons. The authors argue that the dynamics of the basal ganglia circuit cannot be fully characterized by linear properties such as the firing rate or oscillatory activity. In fact, the neuronal spiking stream of the basal ganglia circuit is irregular but has temporal structure. In this context, entropy was introduced as a measure of probabilistic irregularity in the temporal organization of neuronal activity of the basal ganglia, giving place to the entropy hypothesis of basal ganglia pathology. Obtaining a quantitative characterization of irregularity of spike trains from basal ganglia neurons is key to elaborating a new framework of basal ganglia pathophysiology.

  6. High-velocity basal sediment package atop oceanic crust, offshore Cascadia: Impacts on plate boundary processes and fluid migration

    Science.gov (United States)

    Peterson, D. E.; Keranen, K. M.

    2017-12-01

    Differences in fluid pressure and mechanical properties at megathrust boundaries in subduction zones have been proposed to create varying seismogenic behavior. In Cascadia, where large ruptures are possible but little seismicity occurs presently, new seismic transects across the deformation front (COAST cruise; Holbrook et al., 2012) image an unusually high-wavespeed sedimentary unit directly overlying oceanic crust. Wavespeed increases before sediments reach the deformation front, and the well-laminated unit, consistently of 1 km thickness, can be traced for 50 km beneath the accretionary prism before imaging quality declines. Wavespeed is modeled via iterative prestack time migration (PSTM) imaging and increases from 3.5 km/sec on the seaward end of the profile to >5.0 km/s near the deformation front. Landward of the deformation front, wavespeed is low along seaward-dipping thrust faults in the Quaternary accretionary prism, indicative of rapid dewatering along faults. The observed wavespeed of 5.5 km/sec just above subducting crust is consistent with porosity intersects the plate boundary at an oblique angle and changes the degree of hydration of the oceanic plate as it subducts within our area. Fluid flow out of oceanic crust is likely impeded by the low-porosity basal sediment package except along the focused thrust faults. Decollements are present at the top of oceanic basement, at the top of the high-wavespeed basal unit, and within sedimentary strata at higher levels; the decollement at the top of oceanic crust is active at the toe of the deformation front. The basal sedimentary unit appears to be mechanically strong, similar to observations from offshore Sumatra, where strongly consolidated sediments at the deformation front are interpreted to facilitate megathrust rupture to the trench (Hupers et al., 2017). A uniformly strong plate interface at Cascadia may inhibit microseismicity while building stress that is released in great earthquakes.

  7. The edge- and basal-plane-specific electrochemistry of a single-layer graphene sheet

    Science.gov (United States)

    Yuan, Wenjing; Zhou, Yu; Li, Yingru; Li, Chun; Peng, Hailin; Zhang, Jin; Liu, Zhongfan; Dai, Liming; Shi, Gaoquan

    2013-01-01

    Graphene has a unique atom-thick two-dimensional structure and excellent properties, making it attractive for a variety of electrochemical applications, including electrosynthesis, electrochemical sensors or electrocatalysis, and energy conversion and storage. However, the electrochemistry of single-layer graphene has not yet been well understood, possibly due to the technical difficulties in handling individual graphene sheet. Here, we report the electrochemical behavior at single-layer graphene-based electrodes, comparing the basal plane of graphene to its edge. The graphene edge showed 4 orders of magnitude higher specific capacitance, much faster electron transfer rate and stronger electrocatalytic activity than those of graphene basal plane. A convergent diffusion effect was observed at the sub-nanometer thick graphene edge-electrode to accelerate the electrochemical reactions. Coupling with the high conductivity of a high-quality graphene basal plane, graphene edge is an ideal electrode for electrocatalysis and for the storage of capacitive charges. PMID:23896697

  8. Optogenetic Activation of the Sensorimotor Cortex Reveals "Local Inhibitory and Global Excitatory" Inputs to the Basal Ganglia.

    Science.gov (United States)

    Ozaki, Mitsunori; Sano, Hiromi; Sato, Shigeki; Ogura, Mitsuhiro; Mushiake, Hajime; Chiken, Satomi; Nakao, Naoyuki; Nambu, Atsushi

    2017-12-01

    To understand how information from different cortical areas is integrated and processed through the cortico-basal ganglia pathways, we used optogenetics to systematically stimulate the sensorimotor cortex and examined basal ganglia activity. We utilized Thy1-ChR2-YFP transgenic mice, in which channelrhodopsin 2 is robustly expressed in layer V pyramidal neurons. We applied light spots to the sensorimotor cortex in a grid pattern and examined neuronal responses in the globus pallidus (GP) and entopeduncular nucleus (EPN), which are the relay and output nuclei of the basal ganglia, respectively. Light stimulation typically induced a triphasic response composed of early excitation, inhibition, and late excitation in GP/EPN neurons. Other response patterns lacking 1 or 2 of the components were also observed. The distribution of the cortical sites whose stimulation induced a triphasic response was confined, whereas stimulation of the large surrounding areas induced early and late excitation without inhibition. Our results suggest that cortical inputs to the GP/EPN are organized in a "local inhibitory and global excitatory" manner. Such organization seems to be the neuronal basis for information processing through the cortico-basal ganglia pathways, that is, releasing and terminating necessary information at an appropriate timing, while simultaneously suppressing other unnecessary information. © The Author 2017. Published by Oxford University Press.

  9. MRI of the basal ganglia calcification

    International Nuclear Information System (INIS)

    Maeda, Masayuki; Murata, Tetsuhito; Kimura, Hirohiko

    1992-01-01

    MR imaging was performed for 11 patients (9 in Down's syndrome and 2 in idiopathic intracerebral calcification) who showed calcifications in bilateral basal ganglia on CT. High signal intensity in the basal ganglia was found only in one patient with idiopathic intracerebral calcification on T1-weighted image. The calcified areas of all patients in Down's syndrome did not show high signal intensity on T1-weighted image. The exact reasons why MRI exhibits the different signal intensities in calcified tissue on T1-weighted image are unknown. Further clinical investigations will be needed. (author)

  10. Metastatic Basal Cell Carcinoma Accompanying Gorlin Syndrome

    Directory of Open Access Journals (Sweden)

    Yeliz Bilir

    2014-01-01

    Full Text Available Gorlin-Goltz syndrome or basal cell nevus syndrome is an autosomal dominant syndrome characterized by skeletal anomalies, numerous cysts observed in the jaw, and multiple basal cell carcinoma of the skin, which may be accompanied by falx cerebri calcification. Basal cell carcinoma is the most commonly skin tumor with slow clinical course and low metastatic potential. Its concomitance with Gorlin syndrome, resulting from a mutation in a tumor suppressor gene, may substantially change morbidity and mortality. A 66-year-old male patient with a history of recurrent basal cell carcinoma was presented with exophthalmus in the left eye and the lesions localized in the left lateral orbita and left zygomatic area. His physical examination revealed hearing loss, gapped teeth, highly arched palate, and frontal prominence. Left orbital mass, cystic masses at frontal and ethmoidal sinuses, and multiple pulmonary nodules were detected at CT scans. Basal cell carcinoma was diagnosed from biopsy of ethmoid sinus. Based on the clinical and typical radiological characteristics (falx cerebri calcification, bifid costa, and odontogenic cysts, the patient was diagnosed with metastatic skin basal cell carcinoma accompanied by Gorlin syndrome. Our case is a basal cell carcinoma with aggressive course accompanying a rarely seen syndrome.

  11. Calcium imaging of basal forebrain activity during innate and learned behaviors

    Directory of Open Access Journals (Sweden)

    Thomas Clarke Harrison

    2016-05-01

    Full Text Available The basal forebrain (BF plays crucial roles in arousal, attention, and memory, and its impairment is associated with a variety of cognitive deficits. The BF consists of cholinergic, GABAergic, and glutamatergic neurons. Electrical or optogenetic stimulation of BF cholinergic neurons enhances cortical processing and behavioral performance, but the natural activity of these cells during behavior is only beginning to be characterized. Even less is known about GABAergic and glutamatergic neurons. Here, we performed microendoscopic calcium imaging of BF neurons as mice engaged in spontaneous behaviors in their home cages (innate or performed a go/no-go auditory discrimination task (learned. Cholinergic neurons were consistently excited during movement, including running and licking, but GABAergic and glutamatergic neurons exhibited diverse responses. All cell types were activated by overt punishment, either inside or outside of the discrimination task. These findings reveal functional similarities and distinctions between BF cell types during both spontaneous and task-related behaviors.

  12. Nevoid basal cell carcinoma syndrome

    Directory of Open Access Journals (Sweden)

    Kannan Karthiga

    2006-01-01

    Full Text Available Binkley and Johnson first reported this syndrome in 1951. But it was in 1960, Gorlin-Goltz established the association of basal cell epithelioma, jaw cyst and bifid ribs, a combination which is now frequently known as Gorlin-Goltz syndrome as well as Nevoid Basal Cell Carcinoma Syndrome (NBCCS. NBCCS is inherited as an autosomal dominant trait with high penetrance and variable expressivity. NBCCS is characterized by variety of cutaneous, dental, osseous, opthalmic, neurologic and sexual abnormalities. One such case of Gorlin-Goltz syndrome is reported here with good illustrations.

  13. Basal activity of voltage-gated Ca(2+) channels controls the IP3-mediated contraction by α(1)-adrenoceptor stimulation of mouse aorta segments.

    Science.gov (United States)

    Leloup, Arthur J; Van Hove, Cor E; De Meyer, Guido R Y; Schrijvers, Dorien M; Fransen, Paul

    2015-08-05

    α1-Adrenoceptor stimulation of mouse aorta causes intracellular Ca(2+) release from sarcoplasmic reticulum Ca(2+) stores via stimulation of inositoltriphosphate (IP3) receptors. It is hypothesized that this Ca(2+) release from the contractile and IP3-sensitive Ca(2+) store is under the continuous dynamic control of time-independent basal Ca(2+) influx via L-type voltage-gated Ca(2+) channels (LCC) residing in their window voltage range. Mouse aortic segments were α1-adrenoceptor stimulated with phenylephrine in the absence of external Ca(2+) (0Ca) to measure phasic isometric contractions. They gradually decreased with time in 0Ca, were inhibited with 2-aminoethoxydiphenyl borate, and declined with previous membrane potential hyperpolarization (levcromakalim) or with previous inhibition of LCC (diltiazem). Former basal stimulation of LCC with depolarization (15 mM K(+)) or with BAY K8644 increased the subsequent phasic contractions by phenylephrine in 0Ca. Although exogenous NO (diethylamine NONOate) reduced the phasic contractions by phenylephrine, stimulation of endothelial cells with acetylcholine in 0Ca failed to attenuate these phasic contractions. Finally, inhibition of the basal release of NO with N(Ω)-nitro-L-arginine methyl ester also attenuated the phasic contractions by phenylephrine. Results indicated that α1-adrenoceptor stimulation with phenylephrine causes phasic contractions, which are controlled by basal LCC and endothelial NO synthase activity. Endothelial NO release by acetylcholine was absent in 0Ca. Given the growing interest in the active regulation of arterial compliance, the dependence of contractile SR Ca(2+) store-refilling in basal conditions on the activity of LCC and basal eNOS may contribute to a more thorough understanding of physiological mechanisms leading to arterial stiffness. Copyright © 2015. Published by Elsevier B.V.

  14. Clinical significance of diminution of high-density areas in basal cisterns following acute aneurysmal bleeding

    International Nuclear Information System (INIS)

    Matsuzaki, Takayuki; Takeda, Rihei; Nakagawara, Jyoji; Sato, Shigeru; Fujiwara, Hidetoshi

    1983-01-01

    We analyzed the sequential changes in the high density in basal cisterns in the acute stage of aneurysmal bleeding. We could recognize Group 3 (clot or thick layer), according to Fisher's classification, in 66.3% of the intracranial aneurysms at admission (83 cases). In the early stage of an intracranial aneurysm, a subarachnoid hemorrhage (SAH) was detected in all the patients on CT. We evaluated 40 cases of Group 3 sequentially on CT. This investigation showed that 55% of the Grade I--Ii group, 27.3% of the Grade III group, and 11.1% of the Grade IV--V group changed to Group 2(thin or diffuse pattern) in approximately 20 hours on the average. As for the correlation between the high density in basal cisterns and the neurological condition (Hunt and Hess), we found a neurological improvement in the decreased-high-density group. The unchanged- high-density group showed deterioration. Compared with the decreased-high-density group, the unchanged group showed a greater increase in the CVI (Cerebro Ventricular Index). RI ( 111 In) cisternography also showed a disturbance of the CSF circulation. To lower the vasospasm it is important to decrease the high density in an early stage by carrying out CSF. It was considered to be prognostic when a CT scan was performed within 24 hours after SAH. (author)

  15. Raclopride or high-frequency stimulation of the subthalamic nucleus stops cocaine-induced motor stereotypy and restores related alterations in prefrontal basal ganglia circuits.

    Science.gov (United States)

    Aliane, Verena; Pérez, Sylvie; Deniau, Jean-Michel; Kemel, Marie-Louise

    2012-11-01

    Motor stereotypy is a key symptom of various neurological or neuropsychiatric disorders. Neuroleptics or the promising treatment using deep brain stimulation stops stereotypies but the mechanisms underlying their actions are unclear. In rat, motor stereotypies are linked to an imbalance between prefrontal and sensorimotor cortico-basal ganglia circuits. Indeed, cortico-nigral transmission was reduced in the prefrontal but not sensorimotor basal ganglia circuits and dopamine and acetylcholine release was altered in the prefrontal but not sensorimotor territory of the dorsal striatum. Furthermore, cholinergic transmission in the prefrontal territory of the dorsal striatum plays a crucial role in the arrest of motor stereotypy. Here we found that, as previously observed for raclopride, high-frequency stimulation of the subthalamic nucleus (HFS STN) rapidly stopped cocaine-induced motor stereotypies in rat. Importantly, raclopride and HFS STN exerted a strong effect on cocaine-induced alterations in prefrontal basal ganglia circuits. Raclopride restored the cholinergic transmission in the prefrontal territory of the dorsal striatum and the cortico-nigral information transmissions in the prefrontal basal ganglia circuits. HFS STN also restored the N-methyl-d-aspartic-acid-evoked release of acetylcholine and dopamine in the prefrontal territory of the dorsal striatum. However, in contrast to raclopride, HFS STN did not restore the cortico-substantia nigra pars reticulata transmissions but exerted strong inhibitory and excitatory effects on neuronal activity in the prefrontal subdivision of the substantia nigra pars reticulata. Thus, both raclopride and HFS STN stop cocaine-induced motor stereotypy, but exert different effects on the related alterations in the prefrontal basal ganglia circuits. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  16. Learning and memory functions of the Basal Ganglia.

    Science.gov (United States)

    Packard, Mark G; Knowlton, Barbara J

    2002-01-01

    Although the mammalian basal ganglia have long been implicated in motor behavior, it is generally recognized that the behavioral functions of this subcortical group of structures are not exclusively motoric in nature. Extensive evidence now indicates a role for the basal ganglia, in particular the dorsal striatum, in learning and memory. One prominent hypothesis is that this brain region mediates a form of learning in which stimulus-response (S-R) associations or habits are incrementally acquired. Support for this hypothesis is provided by numerous neurobehavioral studies in different mammalian species, including rats, monkeys, and humans. In rats and monkeys, localized brain lesion and pharmacological approaches have been used to examine the role of the basal ganglia in S-R learning. In humans, study of patients with neurodegenerative diseases that compromise the basal ganglia, as well as research using brain neuroimaging techniques, also provide evidence of a role for the basal ganglia in habit learning. Several of these studies have dissociated the role of the basal ganglia in S-R learning from those of a cognitive or declarative medial temporal lobe memory system that includes the hippocampus as a primary component. Evidence suggests that during learning, basal ganglia and medial temporal lobe memory systems are activated simultaneously and that in some learning situations competitive interference exists between these two systems.

  17. Relevance of detail in basal topography for basal slipperiness inversions: a case study on Pine Island Glacier, Antarctica

    Science.gov (United States)

    Kyrke-Smith, Teresa M.; Gudmundsson, G. Hilmar; Farrell, Patrick E.

    2018-04-01

    Given high-resolution satellite-derived surface elevation and velocity data, ice-sheet models generally estimate mechanical basal boundary conditions using surface-to-bed inversion methods. In this work, we address the sensitivity of results from inversion methods to the accuracy of the bed elevation data on Pine Island Glacier. We show that misfit between observations and model output is reduced when high-resolution bed topography is used in the inverse model. By looking at results with a range of detail included in the bed elevation, we consider the separation of basal drag due to the bed topography (form drag) and that due to inherent bed properties (skin drag). The mean value of basal shear stress is reduced when more detailed topography is included in the model. This suggests that without a fully resolved bed a significant amount of the basal shear stress recovered from inversion methods may be due to the unresolved bed topography. However, the spatial structure of the retrieved fields is robust as the bed accuracy is varied; the fields are instead sensitive to the degree of regularisation applied to the inversion. While the implications for the future temporal evolution of PIG are not quantified here directly, our work raises the possibility that skin drag may be overestimated in the current generation of numerical ice-sheet models of this area. These shortcomings could be overcome by inverting simultaneously for both bed topography and basal slipperiness.

  18. Nevoid basal cell carcinoma syndrome

    Science.gov (United States)

    NBCC syndrome; Gorlin-Goltz syndrome; Basal cell nevus syndrome; BCNS; Basal cell cancer - nevoid basal cell carcinoma syndrome ... Nevoid basal cell carcinoma nevus syndrome is a rare genetic ... syndrome is known as PTCH ("patched"). The gene is passed down ...

  19. Cationic Phosphorus Dendrimer Enhances Photodynamic Activity of Rose Bengal against Basal Cell Carcinoma Cell Lines.

    Science.gov (United States)

    Dabrzalska, Monika; Janaszewska, Anna; Zablocka, Maria; Mignani, Serge; Majoral, Jean Pierre; Klajnert-Maculewicz, Barbara

    2017-05-01

    In the last couple of decades, photodynamic therapy emerged as a useful tool in the treatment of basal cell carcinoma. However, it still meets limitations due to unfavorable properties of photosensitizers such as poor solubility or lack of selectivity. Dendrimers, polymers widely studied in biomedical field, may play a role as photosensitizer carriers and improve the efficacy of photodynamic treatment. Here, we describe the evaluation of an electrostatic complex of cationic phosphorus dendrimer and rose bengal in such aspects as singlet oxygen production, cellular uptake, and phototoxicity against three basal cell carcinoma cell lines. Rose bengal-cationic dendrimer complex in molar ratio 5:1 was compared to free rose bengal. Obtained results showed that the singlet oxygen production in aqueous medium was significantly higher for the complex than for free rose bengal. The cellular uptake of the complex was 2-7-fold higher compared to a free photosensitizer. Importantly, rose bengal, rose bengal-dendrimer complex, and dendrimer itself showed no dark toxicity against all three cell lines. Moreover, we observed that phototoxicity of the complex was remarkably enhanced presumably due to high cellular uptake. On the basis of the obtained results, we conclude that rose bengal-cationic dendrimer complex has a potential in photodynamic treatment of basal cell carcinoma.

  20. Pristine Basal- and Edge-Plane-Oriented Molybdenite MoS2 Exhibiting Highly Anisotropic Properties.

    Science.gov (United States)

    Tan, Shu Min; Ambrosi, Adriano; Sofer, Zdenĕk; Huber, Štěpán; Sedmidubský, David; Pumera, Martin

    2015-05-04

    The layered structure of molybdenum disulfide (MoS2 ) is structurally similar to that of graphite, with individual sheets strongly covalently bonded within but held together through weak van der Waals interactions. This results in two distinct surfaces of MoS2 : basal and edge planes. The edge plane was theoretically predicted to be more electroactive than the basal plane, but evidence from direct experimental comparison is elusive. Herein, the first study comparing the two surfaces of MoS2 by using macroscopic crystals is presented. A careful investigation of the electrochemical properties of macroscopic MoS2 pristine crystals with precise control over the exposure of one plane surface, that is, basal plane or edge plane, was performed. These crystals were characterized thoroughly by AFM, Raman spectroscopy, X-ray photoelectron spectroscopy, voltammetry, digital simulation, and DFT calculations. In the Raman spectra, the basal and edge planes show anisotropy in the preferred excitation of E2g and A1g phonon modes, respectively. The edge plane exhibits a much larger heterogeneous electron transfer rate constant k(0) of 4.96×10(-5) and 1.1×10(-3)  cm s(-1) for [Fe(CN)6 ](3-/4-) and [Ru(NH3 )6 ](3+/2+) redox probes, respectively, compared to the basal plane, which yielded k(0) tending towards zero for [Fe(CN)6 ](3-/4-) and about 9.3×10(-4)  cm s(-1) for [Ru(NH3 )6 ](3+/2+) . The industrially important hydrogen evolution reaction follows the trend observed for [Fe(CN)6 ](3-/4-) in that the basal plane is basically inactive. The experimental comparison of the edge and basal planes of MoS2 crystals is supported by DFT calculations. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Prolonged Adaptation to a Low or High Protein Diet Does Not Modulate Basal Muscle Protein Synthesis Rates - A Substudy.

    Science.gov (United States)

    Hursel, Rick; Martens, Eveline A P; Gonnissen, Hanne K J; Hamer, Henrike M; Senden, Joan M G; van Loon, Luc J C; Westerterp-Plantenga, Margriet S

    2015-01-01

    Based on controlled 36 h experiments a higher dietary protein intake causes a positive protein balance and a negative fat balance. A positive net protein balance may support fat free mass accrual. However, few data are available on the impact of more prolonged changes in habitual protein intake on whole-body protein metabolism and basal muscle protein synthesis rates. To assess changes in whole-body protein turnover and basal muscle protein synthesis rates following 12 weeks of adaptation to a low versus high dietary protein intake. A randomized parallel study was performed in 40 subjects who followed either a high protein (2.4 g protein/kg/d) or low protein (0.4 g protein/kg/d) energy-balanced diet (30/35/35% or 5/60/35% energy from protein/carbohydrate/fat) for a period of 12 weeks. A subgroup of 7 men and 8 women (body mass index: 22.8±2.3 kg/m2, age: 24.3±4.9 y) were selected to evaluate the impact of prolonged adaptation to either a high or low protein intake on whole body protein metabolism and basal muscle protein synthesis rates. After the diet, subjects received continuous infusions with L-[ring-2H5]phenylalanine and L-[ring-2H2]tyrosine in an overnight fasted state, with blood samples and muscle biopsies being collected to assess post-absorptive whole-body protein turnover and muscle protein synthesis rates in vivo in humans. After 12 weeks of intervention, whole-body protein balance in the fasted state was more negative in the high protein treatment when compared with the low protein treatment (-4.1±0.5 vs -2.7±0.6 μmol phenylalanine/kg/h;Pprotein breakdown (43.0±4.4 vs 37.8±3.8 μmol phenylalanine/kg/h;Psynthesis (38.9±4.2 vs 35.1±3.6 μmol phenylalanine/kg/h;Pprotein group. Basal muscle protein synthesis rates were maintained on a low vs high protein diet (0.042±0.01 vs 0.045±0.01%/h;P = 0.620). In the overnight fasted state, adaptation to a low-protein intake (0.4 g/kg/d) does not result in a more negative whole-body protein balance and

  2. The development of the region of basal nuclei in fetus using MRI of high field

    International Nuclear Information System (INIS)

    Geng Hequn; Zhang Zhonghe; Liu Shuwei

    2010-01-01

    Objective: To study the developmental process of the region of basal nuclei of postmortem fetuses by 3.0 T and 7.0 T MRI. Methods: One hundred and thirty-one postmortem fetuses of 14 to 40 weeks of gestational age (GA) were scanned by 3.0 T MR, of which 11 fetuses of 14-27 weeks of GA were chosen and scanned by 7.0 T MR. The time when the structures in the region of basal nuclei could be detected and the changes of MR signal intensity were analyzed for MRI of different Tesla. Results: On 3.0 T MRI, the dorsal thalamus could be delineated as early as 14 weeks of GA. The germinal matrix, caudate nucleus, and putamen could be visualized as early as 15 weeks of GA. The globus pallidus could be described as early as 18 weeks of GA, and the internal capsule and external capsule could be shown as early as 20 weeks of GA. The signal of the caudate nucleus during 15-30 weeks of GA was relatively hypointense on T 1 WI and hyperintense on T 2 WI, but during 31-40 weeks of GA, it was relatively hyperintense on T 1 WI and hypointense on T 2 WI. The putamen had a relatively high signal intensity on T 1 WI and low signal intensity on T 2 WI during 15-17 weeks of GA, and it appeared patchy during 18-25 weeks of GA, then it had a relatively low signal intensity on T 1 WI and high signal intensity on T 2 WI during 26-30 weeks of GA, and during 31-40 weeks of GA, its signal intensity was relatively high on T 1 WI and low on T 2 WI. The globus pallidus had a relatively high signal intensity on T 1 WI and low signal intensity on T 2 WI during 20- 40 weeks of GA. Compared to the 3.0 T MRI, the T 2 images of 7.0 T MRI were more clear, and most structures in the region of basal nuclei could be clearly displayed as early as 16 weeks of GA, such as the germinal matrix, caudate nucleus, dorsal thalamus, putamen, globus pallidus, internal capsule, and extemal capsule. The claustrum could be delineated as early as 18 weeks of GA on 7.0 T MRI. Conclusions: 3.0 T MRI could show the development

  3. Basal hypercortisolism and trauma in patients with psychogenic nonepileptic seizures.

    Science.gov (United States)

    Bakvis, Patricia; Spinhoven, Philip; Giltay, Erik J; Kuyk, Jarl; Edelbroek, Peter M; Zitman, Frans G; Roelofs, Karin

    2010-05-01

    Several studies have indicated that psychogenic nonepileptic seizures (PNES) are associated with psychological trauma, but only a few studies have examined the associations with neurobiologic stress systems, such as the hypothalamus-pituitary-adrenal (HPA) axis and its end-product cortisol. We tested several relevant HPA-axis functions in patients with PNES and related them to trauma history. Cortisol awakening curve, basal diurnal cortisol, and negative cortisol feedback (using a 1 mg dexamethasone suppression test) were examined in 18 patients with PNES and 19 matched healthy controls (HCs) using saliva cortisol sampling on two consecutive days at 19 time points. Concomitant sympathetic nervous system (SNS) activity was assessed by analyzing saliva alpha-amylase (sAA). Patients with PNES showed significantly increased basal diurnal cortisol levels compared to HCs. This effect was driven mainly by patients reporting sexual trauma who showed a trend toward higher cortisol levels as compared to patients without a sexual trauma report. Importantly, the increased basal diurnal cortisol levels in patients were not explained by depression, medication, or smoking, or by current seizures or group differences in SNS activity. This is the first study showing that basal hypercortisolism in patients with PNES is independent of the acute occurrence of seizures. In addition, basal hypercortisolism was more pronounced in traumatized patients with PNES as compared to nontraumatized patients with PNES. These findings suggest that HPA-axis activity provides a significant neurobiologic marker for PNES.

  4. Changes in basal ganglia processing of cortical input following magnetic stimulation in Parkinsonism.

    Science.gov (United States)

    Tischler, Hadass; Moran, Anan; Belelovsky, Katya; Bronfeld, Maya; Korngreen, Alon; Bar-Gad, Izhar

    2012-12-01

    Parkinsonism is associated with major changes in neuronal activity throughout the cortico-basal ganglia loop. Current measures quantify changes in baseline neuronal and network activity but do not capture alterations in information propagation throughout the system. Here, we applied a novel non-invasive magnetic stimulation approach using a custom-made mini-coil that enabled us to study transmission of neuronal activity throughout the cortico-basal ganglia loop in both normal and parkinsonian primates. By magnetically perturbing cortical activity while simultaneously recording neuronal responses along the cortico-basal ganglia loop, we were able to directly investigate modifications in descending cortical activity transmission. We found that in both the normal and parkinsonian states, cortical neurons displayed similar multi-phase firing rate modulations in response to magnetic stimulation. However, in the basal ganglia, large synaptically driven stereotypic neuronal modulation was present in the parkinsonian state that was mostly absent in the normal state. The stimulation-induced neuronal activity pattern highlights the change in information propagation along the cortico-basal ganglia loop. Our findings thus point to the role of abnormal dynamic activity transmission rather than changes in baseline activity as a major component in parkinsonian pathophysiology. Moreover, our results hint that the application of transcranial magnetic stimulation (TMS) in human patients of different disorders may result in different neuronal effects than the one induced in normal subjects. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Common features of neural activity during singing and sleep periods in a basal ganglia nucleus critical for vocal learning in a juvenile songbird.

    Directory of Open Access Journals (Sweden)

    Shin Yanagihara

    Full Text Available Reactivations of waking experiences during sleep have been considered fundamental neural processes for memory consolidation. In songbirds, evidence suggests the importance of sleep-related neuronal activity in song system motor pathway nuclei for both juvenile vocal learning and maintenance of adult song. Like those in singing motor nuclei, neurons in the basal ganglia nucleus Area X, part of the basal ganglia-thalamocortical circuit essential for vocal plasticity, exhibit singing-related activity. It is unclear, however, whether Area X neurons show any distinctive spiking activity during sleep similar to that during singing. Here we demonstrate that, during sleep, Area X pallidal neurons exhibit phasic spiking activity, which shares some firing properties with activity during singing. Shorter interspike intervals that almost exclusively occurred during singing in awake periods were also observed during sleep. The level of firing variability was consistently higher during singing and sleep than during awake non-singing states. Moreover, deceleration of firing rate, which is considered to be an important firing property for transmitting signals from Area X to the thalamic nucleus DLM, was observed mainly during sleep as well as during singing. These results suggest that songbird basal ganglia circuitry may be involved in the off-line processing potentially critical for vocal learning during sensorimotor learning phase.

  6. Hierarchical prediction errors in midbrain and basal forebrain during sensory learning.

    Science.gov (United States)

    Iglesias, Sandra; Mathys, Christoph; Brodersen, Kay H; Kasper, Lars; Piccirelli, Marco; den Ouden, Hanneke E M; Stephan, Klaas E

    2013-10-16

    In Bayesian brain theories, hierarchically related prediction errors (PEs) play a central role for predicting sensory inputs and inferring their underlying causes, e.g., the probabilistic structure of the environment and its volatility. Notably, PEs at different hierarchical levels may be encoded by different neuromodulatory transmitters. Here, we tested this possibility in computational fMRI studies of audio-visual learning. Using a hierarchical Bayesian model, we found that low-level PEs about visual stimulus outcome were reflected by widespread activity in visual and supramodal areas but also in the midbrain. In contrast, high-level PEs about stimulus probabilities were encoded by the basal forebrain. These findings were replicated in two groups of healthy volunteers. While our fMRI measures do not reveal the exact neuron types activated in midbrain and basal forebrain, they suggest a dichotomy between neuromodulatory systems, linking dopamine to low-level PEs about stimulus outcome and acetylcholine to more abstract PEs about stimulus probabilities. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Proximity Interactions among Basal Body Components in Trypanosoma brucei Identify Novel Regulators of Basal Body Biogenesis and Inheritance

    Directory of Open Access Journals (Sweden)

    Hung Quang Dang

    2017-01-01

    Full Text Available The basal body shares similar architecture with centrioles in animals and is involved in nucleating flagellar axonemal microtubules in flagellated eukaryotes. The early-branching Trypanosoma brucei possesses a motile flagellum nucleated from the basal body that consists of a mature basal body and an adjacent pro-basal body. Little is known about the basal body proteome and its roles in basal body biogenesis and flagellar axoneme assembly in T. brucei. Here, we report the identification of 14 conserved centriole/basal body protein homologs and 25 trypanosome-specific basal body proteins. These proteins localize to distinct subdomains of the basal body, and several of them form a ring-like structure surrounding the basal body barrel. Functional characterization of representative basal body proteins revealed distinct roles in basal body duplication/separation and flagellar axoneme assembly. Overall, this work identified novel proteins required for basal body duplication and separation and uncovered new functions of conserved basal body proteins in basal body duplication and separation, highlighting an unusual mechanism of basal body biogenesis and inheritance in this early divergent eukaryote.

  8. Sensitivity of grounding line dynamics to basal conditions

    Science.gov (United States)

    Gagliardini, O.; Brondex, J.; Chauveau, G.; Gillet-chaulet, F.; Durand, G.

    2017-12-01

    In the context of a warming climate, the dynamical contribution of Antarctica to future sea level rise is still tainted by high uncertainties. Among the processes entering these uncertainties is the link between basal hydrology, friction and grounding line dynamics. Recent works have shown how sensitive is the response of the grounding line retreat to the choice of the form of the friction law. Indeed, starting from the same initial state, grounding line retreat rates can range over almost two orders of magnitude depending on the friction law formulation.Here, we use a phenomenological law that depends on the water pressure and allows a continuous transition from a Weertman-type friction at low water pressure to a Coulomb-type friction at high water pressure. This friction law depends on two main parameters that control the Weertman and Coulomb regimes. The range of values for these two parameters is only weakly physically constrained, and it can be shown that, for a given basal shear stress, different couples of parameters can conduct to the same sliding velocity. In addition, we show that close to the grounding line where basal water pressure is high, determining these two parameters might conduct to an ill-posed inverse problem with no solution.The aim of this presentation is to discuss a methodology to guide the choice of the two friction parameters and explore the sensitivity of the grounding line dynamics to this initial choice. We present results obtained both on a synthetic configuration used by the Marine Ice Sheet Model Intercomparison exercise and for the Amundsen sea sector using the experiments proposed by InitMIP-Antarctica, the first exercise in a series of ISMIP6 ice-sheet model intercomparison activities.

  9. Computed tomography of calcification of the basal ganglia

    International Nuclear Information System (INIS)

    Park, Churl Min; Suh, Soo Jhi; Kim, Soon Yong

    1981-01-01

    Calcifications of the basal ganglia are rarely found at routine autopsies and in skull radiographs. CT is superior to the plain skull radiographs in detecting intracranial attenuation differences and may be stated to be the method of choice in the diagnosis of intracranial calcifications. Of 5985 brain CT scans performed in Kyung Hee University Hospital during past 3 years, 36 cases were found to have high attenuation lesions suggesting calcifications within basal ganglia. 1. The incidence of basal ganglia calcification on CT scan was about 0.6%. 2. Of these 36 cases, 34 cases were bilateral and the remainder was unilateral. 3. The plain skull films of 23 cases showed visible calcification of basal ganglia in 3 cases (13%). 4. No specific metabolic disease was noted in the cases

  10. Stimulation of ICa by basal PKA activity is facilitated by caveolin-3 in cardiac ventricular myocytes.

    Science.gov (United States)

    Bryant, Simon; Kimura, Tomomi E; Kong, Cherrie H T; Watson, Judy J; Chase, Anabelle; Suleiman, M Saadeh; James, Andrew F; Orchard, Clive H

    2014-03-01

    L-type Ca channels (LTCC), which play a key role in cardiac excitation-contraction coupling, are located predominantly at the transverse (t-) tubules in ventricular myocytes. Caveolae and the protein caveolin-3 (Cav-3) are also present at the t-tubules and have been implicated in localizing a number of signaling molecules, including protein kinase A (PKA) and β2-adrenoceptors. The present study investigated whether disruption of Cav-3 binding to its endogenous binding partners influenced LTCC activity. Ventricular myocytes were isolated from male Wistar rats and LTCC current (ICa) recorded using the whole-cell patch-clamp technique. Incubation of myocytes with a membrane-permeable peptide representing the scaffolding domain of Cav-3 (C3SD) reduced basal ICa amplitude in intact, but not detubulated, myocytes, and attenuated the stimulatory effects of the β2-adrenergic agonist zinterol on ICa. The PKA inhibitor H-89 also reduced basal ICa; however, the inhibitory effects of C3SD and H-89 on basal ICa amplitude were not summative. Under control conditions, myocytes stained with antibody against phosphorylated LTCC (pLTCC) displayed a striated pattern, presumably reflecting localization at the t-tubules. Both C3SD and H-89 reduced pLTCC staining at the z-lines but did not affect staining of total LTCC or Cav-3. These data are consistent with the idea that the effects of C3SD and H-89 share a common pathway, which involves PKA and is maximally inhibited by H-89, and suggest that Cav-3 plays an important role in mediating stimulation of ICa at the t-tubules via PKA-induced phosphorylation under basal conditions, and in response to β2-adrenoceptor stimulation. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. Salivary alpha-amylase: More than an enzyme Investigating confounders of stress-induced and basal amylase activity

    OpenAIRE

    Strahler, Jana

    2010-01-01

    Summary: Salivary alpha-amylase: More than an enzyme - Investigating confounders of stress-induced and basal amylase activity (Dipl.-Psych. Jana Strahler) The hypothalamus-pituitary-adrenal (HPA) axis and the autonomic nervous system (ANS) are two of the major systems playing a role in the adaptation of organisms to developmental changes that threaten homeostasis. The HPA system involves the secretion of glucocorticoids, including cortisol, into the circulatory system. Numerous studies hav...

  12. Axillary basal cell carcinoma in patients with Goltz-Gorlin syndrome: report of basal cell carcinoma in both axilla of a woman with basal cell nevus syndrome and literature review.

    Science.gov (United States)

    Cohen, Philip R

    2014-08-17

    Basal cell carcinoma of the axilla, an area that is not usually exposed to the sun, is rare. Individuals with basal cell nevus syndrome, a disorder associated with a mutation in the patch 1 (PTCH1) gene, develop numerous basal cell carcinomas. To describe a woman with basal cell nevus syndrome who developed a pigmented basal cell carcinoma in each of her axilla and to review the features of axillary basal cell carcinoma patients with Goltz-Gorlin syndrome. Pubmed was used to search the following terms: axillary basal cell carcinoma and basal cell nevus syndrome. The papers and their citations were evaluated. Basal cell nevus syndrome patients with basal cell carcinoma of the axilla were observed in two women; this represents 2.5% (2 of 79) of the patients with axillary basal cell carcinoma. Both women had pigmented tumors that were histologically nonaggressive. The cancers did not recur after curettage or excision. Basal cell carcinoma of the axilla has only been described in 79 individuals; two of the patients were women with pigmented tumors who had basal cell nevus syndrome. Similar to other patients with axillary basal cell carcinoma, the tumors were histologically nonaggressive and did not recur following treatment. Whether PTCH1 gene mutation predisposes basal cell nevus patients to develop axillary basal cell carcinomas remains to be determined.

  13. Oligo-carrageenan kappa increases NADPH, ascorbate and glutathione syntheses and TRR/TRX activities enhancing photosynthesis, basal metabolism, and growth in Eucalyptus trees.

    Science.gov (United States)

    González, Alberto; Moenne, Fabiola; Gómez, Melissa; Sáez, Claudio A; Contreras, Rodrigo A; Moenne, Alejandra

    2014-01-01

    In order to analyze the effect of OC kappa in redox status, photosynthesis, basal metabolism and growth in Eucalyptus globulus, trees were treated with water (control), with OC kappa at 1 mg mL(-1), or treated with inhibitors of NAD(P)H, ascorbate (ASC), and glutathione (GSH) syntheses and thioredoxin reductase (TRR) activity, CHS-828, lycorine, buthionine sulfoximine (BSO), and auranofin, respectively, and with OC kappa, and cultivated for 4 months. Treatment with OC kappa induced an increase in NADPH, ASC, and GSH syntheses, TRR and thioredoxin (TRX) activities, photosynthesis, growth and activities of basal metabolism enzymes such as rubisco, glutamine synthetase (GlnS), adenosine 5'-phosphosulfate reductase (APR), involved in C, N, and S assimilation, respectively, Krebs cycle and purine/pyrimidine synthesis enzymes. Treatment with inhibitors and OC kappa showed that increases in ASC, GSH, and TRR/TRX enhanced NADPH synthesis, increases in NADPH and TRR/TRX enhanced ASC and GSH syntheses, and only the increase in NADPH enhanced TRR/TRX activities. In addition, the increase in NADPH, ASC, GSH, and TRR/TRX enhanced photosynthesis and growth. Moreover, the increase in NADPH, ASC and TRR/TRX enhanced activities of rubisco, Krebs cycle, and purine/pyrimidine synthesis enzymes, the increase in GSH, NADPH, and TRR/TRX enhanced APR activity, and the increase in NADPH and TRR/TRX enhanced GlnS activity. Thus, OC kappa increases NADPH, ASC, and GSH syntheses leading to a more reducing redox status, the increase in NADPH, ASC, GSH syntheses, and TRR/TRX activities are cross-talking events leading to activation of photosynthesis, basal metabolism, and growth in Eucalyptus trees.

  14. Oligo-carrageenan kappa increases NADPH, ascorbate and glutathione syntheses and TRR/TRX activities enhancing photosynthesis, basal metabolism, and growth in Eucalyptus trees

    Directory of Open Access Journals (Sweden)

    Alberto eGonzález

    2014-10-01

    Full Text Available In order to analyze the effect of OC kappa in redox status, photosynthesis, basal metabolism and growth in Eucalyptus globulus, trees were treated with water (control, with OC kappa at 1 mg mL-1, or treated with inhibitors of NAD(PH, ascorbate (ASC and glutathione (GSH syntheses and thioredoxin reductase (TRR activity, CHS-828, lycorine, buthionine sulfoximine (BSO and auranofin, respectively, and with OC kappa, and cultivated for 4 months. Treatment with OC kappa induced an increase in NADPH, ASC, and GSH syntheses, TRR and thioredoxin (TRX activities, photosynthesis, growth and activities of basal metabolism enzymes such as rubisco, glutamine synthetase (GlnS, adenosine 5´-phosphosulfate reductase (APR, involved in C, N and S assimilation, respectively, Krebs cycle and purine/pyrimidine synthesis enzymes. Treatment with inhibitors and OC kappa showed that increases in ASC, GSH and TRR/TRX enhanced NADPH synthesis, increases in NADPH and TRR/TRX enhanced ASC and GSH syntheses, and only the increase in NADPH enhanced TRR/TRX activities. In addition, the increase in NADPH, ASC, GSH and TRR/TRX enhanced photosynthesis and growth. Moreover, the increase in NADPH, ASC and TRR/TRX enhanced activities of rubisco, Krebs cycle and purine/pyrimidine synthesis enzymes, the increase in GSH, NADPH, and TRR/TRX enhanced APR activity, and the increase in NADPH and TRR/TRX enhanced GlnS activity. Thus, OC kappa increases NADPH, ASC and GSH syntheses leading to a more reducing redox status, the increase in NADPH, ASC, GSH syntheses and TRR/TRX activities are cross-talking events leading to activation of photosynthesis, basal metabolism and growth in Eucalyptus trees.

  15. Soil Microbial Biomass, Basal Respiration and Enzyme Activity of Main Forest Types in the Qinling Mountains

    Science.gov (United States)

    Cheng, Fei; Peng, Xiaobang; Zhao, Peng; Yuan, Jie; Zhong, Chonggao; Cheng, Yalong; Cui, Cui; Zhang, Shuoxin

    2013-01-01

    Different forest types exert essential impacts on soil physical-chemical characteristics by dominant tree species producing diverse litters and root exudates, thereby further regulating size and activity of soil microbial communities. However, the study accuracy is usually restricted by differences in climate, soil type and forest age. Our objective is to precisely quantify soil microbial biomass, basal respiration and enzyme activity of five natural secondary forest (NSF) types with the same stand age and soil type in a small climate region and to evaluate relationship between soil microbial and physical-chemical characters. We determined soil physical-chemical indices and used the chloroform fumigation-extraction method, alkali absorption method and titration or colorimetry to obtain the microbial data. Our results showed that soil physical-chemical characters remarkably differed among the NSFs. Microbial biomass carbon (Cmic) was the highest in wilson spruce soils, while microbial biomass nitrogen (Nmic) was the highest in sharptooth oak soils. Moreover, the highest basal respiration was found in the spruce soils, but mixed, Chinese pine and spruce stands exhibited a higher soil qCO2. The spruce soils had the highest Cmic/Nmic ratio, the greatest Nmic/TN and Cmic/Corg ratios were found in the oak soils. Additionally, the spruce soils had the maximum invertase activity and the minimum urease and catalase activities, but the maximum urease and catalase activities were found in the mixed stand. The Pearson correlation and principle component analyses revealed that the soils of spruce and oak stands obviously discriminated from other NSFs, whereas the others were similar. This suggested that the forest types affected soil microbial properties significantly due to differences in soil physical-chemical features. PMID:23840671

  16. MOLECULAR BASIS OF EPIDERMAL GROWTH FACTOR RECEPTOR AND CYCLIN E EXPRESSION INTERDEPENDENCE IN BASAL-LIKE SUBTYPE OF INVASIVE BREAST CARCINOMA.

    Science.gov (United States)

    Mariamidze, A; Gogiashvili, L; Khardzeishvili, O; Javakhishvili, T; Makaridze, D

    2018-03-01

    Aim of the study was the simultaneous assessment of EGFR and Cyclin E in "basal-like" carcinoma group, in order to establish their interactivity in the aspect of the age and grade of the tumor, taking into account the common parallel HER2+ samples. The study involved postoperative and/or biopsy material (paraffin blocks) of 237 patients from archived data, who were operated due to breast cancer (National Cancer Center of Tbilisi, 2008-2012 years). In TNBC group and "basal-like" tumor subgroup expression of ESFR, Cyclin E and Cytokeratins 5/6 and 17 were shown advanced activity of processes and high dependence to patients age. Taking into account all above mentioned, the immunohistochemical profile of "basal-like" type of breast cancer is defined mostly by sensitivity to cytokeratins CK5,6/17 and EGFR. In addition, the defected synthesis and activity of the latter, which is actually observed in "basal-like" carcinoma, leads to increased malignancy grade and mitotic activity, which creates the phenotypic and group characteristics for this type of carcinomas overall.

  17. Global dysrhythmia of cerebro-basal ganglia-cerebellar networks underlies motor tics following striatal disinhibition.

    Science.gov (United States)

    McCairn, Kevin W; Iriki, Atsushi; Isoda, Masaki

    2013-01-09

    Motor tics, a cardinal symptom of Tourette syndrome (TS), are hypothesized to arise from abnormalities within cerebro-basal ganglia circuits. Yet noninvasive neuroimaging of TS has previously identified robust activation in the cerebellum. To date, electrophysiological properties of cerebellar activation and its role in basal ganglia-mediated tic expression remain unknown. We performed multisite, multielectrode recordings of single-unit activity and local field potentials from the cerebellum, basal ganglia, and primary motor cortex using a pharmacologic monkey model of motor tics/TS. Following microinjections of bicuculline into the sensorimotor putamen, periodic tics occurred predominantly in the orofacial region, and a sizable number of cerebellar neurons showed phasic changes in activity associated with tic episodes. Specifically, 64% of the recorded cerebellar cortex neurons exhibited increases in activity, and 85% of the dentate nucleus neurons displayed excitatory, inhibitory, or multiphasic responses. Critically, abnormal discharges of cerebellar cortex neurons and excitatory-type dentate neurons mostly preceded behavioral tic onset, indicating their central origins. Latencies of pathological activity in the cerebellum and primary motor cortex substantially overlapped, suggesting that aberrant signals may be traveling along divergent pathways to these structures from the basal ganglia. Furthermore, the occurrence of tic movement was most closely associated with local field potential spikes in the cerebellum and primary motor cortex, implying that these structures may function as a gate to release overt tic movements. These findings indicate that tic-generating networks in basal ganglia mediated tic disorders extend beyond classical cerebro-basal ganglia circuits, leading to global network dysrhythmia including cerebellar circuits.

  18. Registration of an oilseed sunflower germplasm line HA-BSR1 highly tolerant to Sclerotinia basal stalk rot

    Science.gov (United States)

    Basal stalk rot (BSR) caused by Sclerotinia sclerotiorum (Lib.) de Bary is a devastating disease that causes a significant damage to worldwide sunflower (Helianthus annuus L.) production by reducing seed yield and quality. The objective of this research was to develop highly BSR tolerant sunflower g...

  19. Cortical stimulation evokes abnormal responses in the dopamine-depleted rat basal ganglia.

    Science.gov (United States)

    Kita, Hitoshi; Kita, Takako

    2011-07-13

    The motor cortex (MC) sends massive projections to the basal ganglia. Motor disabilities in patients and animal models of Parkinson's disease (PD) may be caused by dopamine (DA)-depleted basal ganglia that abnormally process the information originating from MC. To study how DA depletion alters signal transfer in the basal ganglia, MC stimulation-induced (MC-induced) unitary responses were recorded from the basal ganglia of control and 6-hydroxydopamine-treated hemi-parkinsonian rats anesthetized with isoflurane. This report describes new findings about how DA depletion alters MC-induced responses. MC stimulation evokes an excitation in normally quiescent striatal (Str) neurons projecting to the globus pallidus external segment (GPe). After DA-depletion, the spontaneous firing of Str-GPe neurons increases, and MC stimulation evokes a shorter latency excitation followed by a long-lasting inhibition that was invisible under normal conditions. The increased firing activity and the newly exposed long inhibition generate tonic inhibition and a disfacilitation in GPe. The disfacilitation in GPe is then amplified in basal ganglia circuitry and generates a powerful long inhibition in the basal ganglia output nucleus, the globus pallidus internal segment. Intra-Str injections of a behaviorally effective dose of DA precursor l-3,4-dihydroxyphenylalanine effectively reversed these changes. These newly observed mechanisms also support the generation of pauses and burst activity commonly observed in the basal ganglia of parkinsonian subjects. These results suggest that the generation of abnormal response sequences in the basal ganglia contributes to the development of motor disabilities in PD and that intra-Str DA supplements effectively suppress abnormal signal transfer.

  20. Tumor Architecture and Notch Signaling Modulate Drug Response in Basal Cell Carcinoma.

    Science.gov (United States)

    Eberl, Markus; Mangelberger, Doris; Swanson, Jacob B; Verhaegen, Monique E; Harms, Paul W; Frohm, Marcus L; Dlugosz, Andrzej A; Wong, Sunny Y

    2018-02-12

    Hedgehog (Hh) pathway inhibitors such as vismodegib are highly effective for treating basal cell carcinoma (BCC); however, residual tumor cells frequently persist and regenerate the primary tumor upon drug discontinuation. Here, we show that BCCs are organized into two molecularly and functionally distinct compartments. Whereas interior Hh + /Notch + suprabasal cells undergo apoptosis in response to vismodegib, peripheral Hh +++ /Notch - basal cells survive throughout treatment. Inhibiting Notch specifically promotes tumor persistence without causing drug resistance, while activating Notch is sufficient to regress already established lesions. Altogether, these findings suggest that the three-dimensional architecture of BCCs establishes a natural hierarchy of drug response in the tumor and that this hierarchy can be overcome, for better or worse, by modulating Notch. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Imiquimod activates p53-dependent apoptosis in a human basal cell carcinoma cell line.

    Science.gov (United States)

    Huang, Shi-Wei; Chang, Shu-Hao; Mu, Szu-Wei; Jiang, Hsin-Yi; Wang, Sin-Ting; Kao, Jun-Kai; Huang, Jau-Ling; Wu, Chun-Ying; Chen, Yi-Ju; Shieh, Jeng-Jer

    2016-03-01

    The tumor suppressor p53 controls DNA repair, cell cycle, apoptosis, autophagy and numerous other cellular processes. Imiquimod (IMQ), a synthetic toll-like receptor (TLR) 7 ligand for the treatment of superficial basal cell carcinoma (BCC), eliminates cancer cells by activating cell-mediated immunity and directly inducing apoptosis and autophagy in cancer cells. To evaluate the role of p53 in IMQ-induced cell death in skin cancer cells. The expression, phosphorylation and subcellular localization of p53 were detected by real-time PCR, luciferase reporter assay, cycloheximide chase analysis, immunoblotting and immunocytochemistry. Using BCC/KMC1 cell line as a model, the upstream signaling of p53 activation was dissected by over-expression of TLR7/8, the addition of ROS scavenger, ATM/ATR inhibitors and pan-caspase inhibitor. The role of p53 in IMQ-induced apoptosis and autophagy was assessed by genetically silencing p53 and evaluated by a DNA content assay, immunoblotting, LC3 puncta detection and acridine orange staining. IMQ induced p53 mRNA expression and protein accumulation, increased Ser15 phosphorylation, promoted nuclear translocation and up-regulated its target genes in skin cancer cells in a TLR7/8-independent manner. In BCC/KMC1 cells, the induction of p53 by IMQ was achieved through increased ROS production to stimulate the ATM/ATR-Chk1/Chk2 axis but was not mediated by inducing DNA damage. The pharmacological inhibition of ATM/ATR significantly suppressed IMQ-induced p53 activation and apoptosis. Silencing of p53 significantly decreased the IMQ-induced caspase cascade activation and apoptosis but enhanced autophagy. Mutant p53 skin cancer cell lines were more resistant to IMQ-induced apoptosis than wildtype p53 skin cancer cell lines. IMQ induced ROS production to stimulate ATM/ATR pathways and contributed to p53-dependent apoptosis in a skin basal cell carcinoma cell line BCC/KMC1. Copyright © 2015 Japanese Society for Investigative Dermatology

  2. Basal Cell Carcinoma: 10 Years of Experience

    International Nuclear Information System (INIS)

    Cigna, E.; Tarallo, M.; Maruccia, M.; Sorvillo, V.; Pollastrini, A.; Scuderi, N.

    2011-01-01

    Introduction. Basal cell carcinoma (BCC) is a locally invasive malignant epidermal tumour. Incidence is increasing by 10% per year; incidence of metastases is minimal, but relapses are frequent (40%-50%). The complete excision of the BCC allows reduction of relapse. Materials and Methods. The study cohort consists of 1123 patients underwent surgery for basal cell carcinoma between 1999 and 2009. Patient and tumor characteristics recorded are: age; gender; localization (head and neck, trunk, and upper and lower extremities), tumor size, excisional margins adopted, and relapses. Results. The study considered a group of 1123 patients affected by basal cell carcinoma. Relapses occurred in 30 cases (2,67%), 27 out of 30 relapses occurred in noble areas, where peripheral margin was <3mm. Incompletely excised basal cell carcinoma occurred in 21 patients (1,87%) and were treated with an additional excision. Discussion. Although guidelines indicate 3mm peripheral margin of excision in BCC <2cm, in our experience, a margin of less than 5mm results in a high risk of incomplete excisions

  3. Prolonged Adaptation to a Low or High Protein Diet Does Not Modulate Basal Muscle Protein Synthesis Rates - A Substudy.

    Directory of Open Access Journals (Sweden)

    Rick Hursel

    Full Text Available Based on controlled 36 h experiments a higher dietary protein intake causes a positive protein balance and a negative fat balance. A positive net protein balance may support fat free mass accrual. However, few data are available on the impact of more prolonged changes in habitual protein intake on whole-body protein metabolism and basal muscle protein synthesis rates.To assess changes in whole-body protein turnover and basal muscle protein synthesis rates following 12 weeks of adaptation to a low versus high dietary protein intake.A randomized parallel study was performed in 40 subjects who followed either a high protein (2.4 g protein/kg/d or low protein (0.4 g protein/kg/d energy-balanced diet (30/35/35% or 5/60/35% energy from protein/carbohydrate/fat for a period of 12 weeks. A subgroup of 7 men and 8 women (body mass index: 22.8±2.3 kg/m2, age: 24.3±4.9 y were selected to evaluate the impact of prolonged adaptation to either a high or low protein intake on whole body protein metabolism and basal muscle protein synthesis rates. After the diet, subjects received continuous infusions with L-[ring-2H5]phenylalanine and L-[ring-2H2]tyrosine in an overnight fasted state, with blood samples and muscle biopsies being collected to assess post-absorptive whole-body protein turnover and muscle protein synthesis rates in vivo in humans.After 12 weeks of intervention, whole-body protein balance in the fasted state was more negative in the high protein treatment when compared with the low protein treatment (-4.1±0.5 vs -2.7±0.6 μmol phenylalanine/kg/h;P<0.001. Whole-body protein breakdown (43.0±4.4 vs 37.8±3.8 μmol phenylalanine/kg/h;P<0.03, synthesis (38.9±4.2 vs 35.1±3.6 μmol phenylalanine/kg/h;P<0.01 and phenylalanine hydroxylation rates (4.1±0.6 vs 2.7±0.6 μmol phenylalanine/kg/h;P<0.001 were significantly higher in the high vs low protein group. Basal muscle protein synthesis rates were maintained on a low vs high protein diet (0.042

  4. TASK Channels on Basal Forebrain Cholinergic Neurons Modulate Electrocortical Signatures of Arousal by Histamine.

    Science.gov (United States)

    Vu, Michael T; Du, Guizhi; Bayliss, Douglas A; Horner, Richard L

    2015-10-07

    Basal forebrain cholinergic neurons are the main source of cortical acetylcholine, and their activation by histamine elicits cortical arousal. TWIK-like acid-sensitive K(+) (TASK) channels modulate neuronal excitability and are expressed on basal forebrain cholinergic neurons, but the role of TASK channels in the histamine-basal forebrain cholinergic arousal circuit is unknown. We first expressed TASK channel subunits and histamine Type 1 receptors in HEK cells. Application of histamine in vitro inhibited the acid-sensitive K(+) current, indicating a functionally coupled signaling mechanism. We then studied the role of TASK channels in modulating electrocortical activity in vivo using freely behaving wild-type (n = 12) and ChAT-Cre:TASK(f/f) mice (n = 12), the latter lacking TASK-1/3 channels on cholinergic neurons. TASK channel deletion on cholinergic neurons significantly altered endogenous electroencephalogram oscillations in multiple frequency bands. We then identified the effect of TASK channel deletion during microperfusion of histamine into the basal forebrain. In non-rapid eye movement sleep, TASK channel deletion on cholinergic neurons significantly attenuated the histamine-induced increase in 30-50 Hz activity, consistent with TASK channels contributing to histamine action on basal forebrain cholinergic neurons. In contrast, during active wakefulness, histamine significantly increased 30-50 Hz activity in ChAT-Cre:TASK(f/f) mice but not wild-type mice, showing that the histamine response depended upon the prevailing cortical arousal state. In summary, we identify TASK channel modulation in response to histamine receptor activation in vitro, as well as a role of TASK channels on cholinergic neurons in modulating endogenous oscillations in the electroencephalogram and the electrocortical response to histamine at the basal forebrain in vivo. Attentive states and cognitive function are associated with the generation of γ EEG activity. Basal forebrain

  5. Somatic Cell Fusions Reveal Extensive Heterogeneity in Basal-like Breast Cancer

    Directory of Open Access Journals (Sweden)

    Ying Su

    2015-06-01

    Full Text Available Basal-like and luminal breast tumors have distinct clinical behavior and molecular profiles, yet the underlying mechanisms are poorly defined. To interrogate processes that determine these distinct phenotypes and their inheritance pattern, we generated somatic cell fusions and performed integrated genetic and epigenetic (DNA methylation and chromatin profiling. We found that the basal-like trait is generally dominant and is largely defined by epigenetic repression of luminal transcription factors. Definition of super-enhancers highlighted a core program common in luminal cells but a high degree of heterogeneity in basal-like breast cancers that correlates with clinical outcome. We also found that protein extracts of basal-like cells are sufficient to induce a luminal-to-basal phenotypic switch, implying a trigger of basal-like autoregulatory circuits. We determined that KDM6A might be required for luminal-basal fusions, and we identified EN1, TBX18, and TCF4 as candidate transcriptional regulators of the luminal-to-basal switch. Our findings highlight the remarkable epigenetic plasticity of breast cancer cells.

  6. Analeptic activity produced by TRH microinjection into basal forebrain area of the rat

    International Nuclear Information System (INIS)

    Horita, A.; Carino, M.A.; Lai, H.

    1986-01-01

    Earlier, Kalivas and Horita demonstrated that the analeptic effect of TRH was mediated in part by cholinergic neurons in the medial septum-diagonal band of Broca (MS-DBB). Since the MS-DBB constitutes part of the cholinergic basal forebrain system, the present study investigated whether the area designated as the n. basalis of Meynert (NBM) was also sensitive to TRH in producing an antipentobarbital effect. Saline or TRH (0.5 μl) was microinjected via bilateral stainless steel cannulae implanted stereotaxically into the NBM using the coordinates of Wenk et al. Accuracy of cannula placement was confirmed by histological examination. Rats treated with PB (40 mg/kg, i.p.) lost their righting reflex for 130 +/- 28 min. Intrabasalis injection of TRH (but not saline) in doses of 0.1-1.0 μg exerted analeptic activity as follows: 0.1 μg = 81 +/- 21 min; 0.5 μg = 65 +/- 19 min; 1.0 μg = 45 +/- 10 min. All of these doses exerted significant shortening of narcosis duration of pentobarbitalized rats. The analeptic effect of TRH was blocked by atropine pretreatment, indicating that it was mediated via cholinergic mechanisms. High affinity, sodium-dependent 3 H-choline uptake by cortical synaptosomes prepared from these animals was also increased by TRH. These results suggest that the cholinergic neurons of NBM are highly sensitive to TRH and contributes to the analeptic effect of TRH

  7. The effect of high mesencephalic transection (cerveau isolé) and pentobarbital on basal forebrain mechanisms of EEG synchronization.

    Science.gov (United States)

    Obál, F; Benedek, G; Szikszay, M; Obál, F

    1979-01-01

    A study was made of the effects of high mesencephalic transection (cerveau isolé) and low doses of pentobarbital on the cortical synchronizations elicited in acute immobilized cats by (a) low frequency stimulation of the lateral hypothalamus (HL) and nucleus ventralis anterior thalami (VA) and (b) by low and high frequency stimulation of the laterobasal preoptic region (RPO) and olfactory tubercle (TbOf). The results obtained were as follows: (1) The synchronizations induced by basal forebrain stimulations were found to survive in acute cerveau isolé cats, moreover, even a facilitation of the synchronizing effect were observed. (2) A gradual facilitation was observed upon TbOf and RPO stimulation, while in the case of VA and HL stimulations, the facilitation appeared immediately after the transection. (3) Low doses of pentobarbital depressed the cortical effects of TbOf stimulation, while an increase of the synchronizing effect of low frequency VA and HL stimulation was found. The observations suggested that (i) the synchronizing mechanism in the ventral part of the basal forebrain (RPO and TbOf) differs from that of the thalamus and HL; (ii) the basal forebrain synchronizing mechanism is effective without the contribution of the brain stem; (iii) the mechanism responsible for the synchronizing effect of low frequency HL stimulation is similar as that described for the thalamus.

  8. Cholinergic Inputs from Basal Forebrain Add an Excitatory Bias to Odor Coding in the Olfactory Bulb

    Science.gov (United States)

    Rothermel, Markus; Carey, Ryan M.; Puche, Adam; Shipley, Michael T.

    2014-01-01

    Cholinergic modulation of central circuits is associated with active sensation, attention, and learning, yet the neural circuits and temporal dynamics underlying cholinergic effects on sensory processing remain unclear. Understanding the effects of cholinergic modulation on particular circuits is complicated by the widespread projections of cholinergic neurons to telencephalic structures that themselves are highly interconnected. Here we examined how cholinergic projections from basal forebrain to the olfactory bulb (OB) modulate output from the first stage of sensory processing in the mouse olfactory system. By optogenetically activating their axons directly in the OB, we found that cholinergic projections from basal forebrain regulate OB output by increasing the spike output of presumptive mitral/tufted cells. Cholinergic stimulation increased mitral/tufted cell spiking in the absence of inhalation-driven sensory input and further increased spiking responses to inhalation of odorless air and to odorants. This modulation was rapid and transient, was dependent on local cholinergic signaling in the OB, and differed from modulation by optogenetic activation of cholinergic neurons in basal forebrain, which led to a mixture of mitral/tufted cell excitation and suppression. Finally, bulbar cholinergic enhancement of mitral/tufted cell odorant responses was robust and occurred independent of the strength or even polarity of the odorant-evoked response, indicating that cholinergic modulation adds an excitatory bias to mitral/tufted cells as opposed to increasing response gain or sharpening response spectra. These results are consistent with a role for the basal forebrain cholinergic system in dynamically regulating the sensitivity to or salience of odors during active sensing of the olfactory environment. PMID:24672011

  9. Induced resistance: an enhancement of basal resistance?

    NARCIS (Netherlands)

    Vos, M. de; Robben, C.; Pelt, J.A. van; Loon, L.C. van; Pieterse, C.M.J.

    2002-01-01

    Upon primary pathogen attack, plants activate resistance mechanisms at the site of infection. Besides this so-called basal resistance, plants have also the ability to enhance their defensive capacity against future pathogen attack. There are at least two types of biologically induced resistance.

  10. Basal Ganglia Activity Mirrors a Benefit of Action and Reward on Long-Lasting Event Memory.

    Science.gov (United States)

    Koster, Raphael; Guitart-Masip, Marc; Dolan, Raymond J; Düzel, Emrah

    2015-12-01

    The expectation of reward is known to enhance a consolidation of long-term memory for events. We tested whether this effect is driven by positive valence or action requirements tied to expected reward. Using a functional magnetic resonance imaging (fMRI) paradigm in young adults, novel images predicted gain or loss outcomes, which in turn were either obtained or avoided by action or inaction. After 24 h, memory for these images reflected a benefit of action as well as a congruence of action requirements and valence, namely, action for reward and inaction for avoidance. fMRI responses in the hippocampus, a region known to be critical for long-term memory function, reflected the anticipation of inaction. In contrast, activity in the putamen mirrored the congruence of action requirement and valence, whereas other basal ganglia regions mirrored overall action benefits on long-lasting memory. The findings indicate a novel type of functional division between the hippocampus and the basal ganglia in the motivational regulation of long-term memory consolidation, which favors remembering events that are worth acting for. © The Author 2015. Published by Oxford University Press.

  11. Functional neuroanatomy of the basal ganglia.

    Science.gov (United States)

    Lanciego, José L; Luquin, Natasha; Obeso, José A

    2012-12-01

    The "basal ganglia" refers to a group of subcortical nuclei responsible primarily for motor control, as well as other roles such as motor learning, executive functions and behaviors, and emotions. Proposed more than two decades ago, the classical basal ganglia model shows how information flows through the basal ganglia back to the cortex through two pathways with opposing effects for the proper execution of movement. Although much of the model has remained, the model has been modified and amplified with the emergence of new data. Furthermore, parallel circuits subserve the other functions of the basal ganglia engaging associative and limbic territories. Disruption of the basal ganglia network forms the basis for several movement disorders. This article provides a comprehensive account of basal ganglia functional anatomy and chemistry and the major pathophysiological changes underlying disorders of movement. We try to answer three key questions related to the basal ganglia, as follows: What are the basal ganglia? What are they made of? How do they work? Some insight on the canonical basal ganglia model is provided, together with a selection of paradoxes and some views over the horizon in the field.

  12. SP-transcription factors are involved in basal MVP promoter activity and its stimulation by HDAC inhibitors.

    Science.gov (United States)

    Steiner, Elisabeth; Holzmann, Klaus; Pirker, Christine; Elbling, Leonilla; Micksche, Michael; Berger, Walter

    2004-04-23

    The major vault protein (MVP) has been implicated in multidrug resistance, cellular transport, and malignant transformation. In this study we aimed to identify crucial MVP promoter elements that regulate MVP expression. By mutation as well as deletion analysis a conserved proximal GC-box element was demonstrated to be essential for basal human MVP promoter transactivation. Binding of Sp-family transcription factors but not AP2 to this element in vitro and in vivo was shown by EMSA and ChIP assays, respectively. Inhibition of GC-box binding by a dominant-negative Sp1-variant and by mithramycin A distinctly attenuated MVP promoter activity. In Sp-null Drosophila cells, the silent human MVP promoter was transactivated by several human Sp-family members. In human cells the MVP promoter was potently stimulated by the histone deacetylase (HDAC) inhibitors butyrate (NaB) and trichostatin A (TSA), resulting in enhanced MVP expression. This stimulation was substantially decreased by mutation of the single GC-box and by application of mithramycin A. Treatment with HDAC inhibitors led to a distinct decrease of Sp1 but increase of Sp3 binding in vivo to the respective promoter sequence as demonstrated by ChIP assays. Summarising, this study identifies variations in Sp-transcription factor binding to a single proximal GC-box element as critical for basal MVP promoter activation and its stimulation by HDAC inhibitors.

  13. Deep-Brain Stimulation for Basal Ganglia Disorders.

    Science.gov (United States)

    Wichmann, Thomas; Delong, Mahlon R

    2011-07-01

    The realization that medications used to treat movement disorders and psychiatric conditions of basal ganglia origin have significant shortcomings, as well as advances in the understanding of the functional organization of the brain, has led to a renaissance in functional neurosurgery, and particularly the use of deep brain stimulation (DBS). Movement disorders are now routinely being treated with DBS of 'motor' portions of the basal ganglia output nuclei, specifically the subthalamic nucleus and the internal pallidal segment. These procedures are highly effective and generally safe. Use of DBS is also being explored in the treatment of neuropsychiatric disorders, with targeting of the 'limbic' basal ganglia-thalamocortical circuitry. The results of these procedures are also encouraging, but many unanswered questions remain in this emerging field. This review summarizes the scientific rationale and practical aspects of using DBS for neurologic and neuropsychiatric disorders.

  14. Cholinergic basal forebrain structures are not essential for mediation of the arousing action of glutamate.

    Science.gov (United States)

    Lelkes, Zoltán; Abdurakhmanova, Shamsiiat; Porkka-Heiskanen, Tarja

    2017-09-18

    The cholinergic basal forebrain contributes to cortical activation and receives rich innervations from the ascending activating system. It is involved in the mediation of the arousing actions of noradrenaline and histamine. Glutamatergic stimulation in the basal forebrain results in cortical acetylcholine release and suppression of sleep. However, it is not known to what extent the cholinergic versus non-cholinergic basal forebrain projection neurones contribute to the arousing action of glutamate. To clarify this question, we administered N-methyl-D-aspartate (NMDA), a glutamate agonist, into the basal forebrain in intact rats and after destruction of the cholinergic cells in the basal forebrain with 192 immunoglobulin (Ig)G-saporin. In eight Han-Wistar rats with implanted electroencephalogram/electromyogram (EEG/EMG) electrodes and guide cannulas for microdialysis probes, 0.23 μg 192 IgG-saporin was administered into the basal forebrain, while the eight control animals received artificial cerebrospinal fluid. Two weeks later, a microdialysis probe targeted into the basal forebrain was perfused with cerebrospinal fluid on the baseline day and for 3 h with 0.3 mmNMDA on the subsequent day. Sleep-wake activity was recorded for 24 h on both days. NMDA exhibited a robust arousing effect in both the intact and the lesioned rats. Wakefulness was increased and both non-REM and REM sleep were decreased significantly during the 3-h NMDA perfusion. Destruction of the basal forebrain cholinergic neurones did not abolish the wake-enhancing action of NMDA. Thus, the cholinergic basal forebrain structures are not essential for the mediation of the arousing action of glutamate. © 2017 European Sleep Research Society.

  15. High basal metabolic rate does not elevate oxidative stress during reproduction in laboratory mice.

    Science.gov (United States)

    Brzęk, Paweł; Książek, Aneta; Ołdakowski, Łukasz; Konarzewski, Marek

    2014-05-01

    Increased oxidative stress (OS) has been suggested as a physiological cost of reproduction. However, previous studies reported ambiguous results, with some even showing a reduction of oxidative damage during reproduction. We tested whether the link between reproduction and OS is mediated by basal metabolic rate (BMR), which has been hypothesized to affect both the rate of radical oxygen species production and antioxidative capacity. We studied the effect of reproduction on OS in females of laboratory mice divergently selected for high (H-BMR) and low (L-BMR) BMR, previously shown to differ with respect to parental investment. Non-reproducing L-BMR females showed higher oxidative damage to lipids (quantified as the level of malondialdehyde in internal organ tissues) and DNA (quantified as the level of 8-oxodG in blood serum) than H-BMR females. Reproduction did not affect oxidative damage to lipids in either line; however, it reduced damage to DNA in L-BMR females. Reproduction increased catalase activity in liver (significantly stronger in L-BMR females) and decreased it in kidneys. We conclude that the effect of reproduction on OS depends on the initial variation in BMR and varies between studied internal organs and markers of OS.

  16. Defined Conditions for the Isolation and Expansion of Basal Prostate Progenitor Cells of Mouse and Human Origin

    Directory of Open Access Journals (Sweden)

    Thomas Höfner

    2015-03-01

    Full Text Available Methods to isolate and culture primary prostate epithelial stem/progenitor cells (PESCs have proven difficult and ineffective. Here, we present a method to grow and expand both murine and human basal PESCs long term in serum- and feeder-free conditions. The method enriches for adherent mouse basal PESCs with a Lin−SCA-1+CD49f+TROP2high phenotype. Progesterone and sodium selenite are additionally required for the growth of human Lin−CD49f+TROP2high PESCs. The gene-expression profiles of expanded basal PESCs show similarities to ESCs, and NF-kB function is critical for epithelial differentiation of sphere-cultured PESCs. When transplanted in combination with urogenital sinus mesenchyme, expanded mouse and human PESCs generate ectopic prostatic tubules, demonstrating their stem cell activity in vivo. This novel method will facilitate the molecular, genomic, and functional characterization of normal and pathologic prostate glands of mouse and human origin.

  17. The human airway epithelial basal cell transcriptome.

    Directory of Open Access Journals (Sweden)

    Neil R Hackett

    2011-05-01

    Full Text Available The human airway epithelium consists of 4 major cell types: ciliated, secretory, columnar and basal cells. During natural turnover and in response to injury, the airway basal cells function as stem/progenitor cells for the other airway cell types. The objective of this study is to better understand human airway epithelial basal cell biology by defining the gene expression signature of this cell population.Bronchial brushing was used to obtain airway epithelium from healthy nonsmokers. Microarrays were used to assess the transcriptome of basal cells purified from the airway epithelium in comparison to the transcriptome of the differentiated airway epithelium. This analysis identified the "human airway basal cell signature" as 1,161 unique genes with >5-fold higher expression level in basal cells compared to differentiated epithelium. The basal cell signature was suppressed when the basal cells differentiated into a ciliated airway epithelium in vitro. The basal cell signature displayed overlap with genes expressed in basal-like cells from other human tissues and with that of murine airway basal cells. Consistent with self-modulation as well as signaling to other airway cell types, the human airway basal cell signature was characterized by genes encoding extracellular matrix components, growth factors and growth factor receptors, including genes related to the EGF and VEGF pathways. Interestingly, while the basal cell signature overlaps that of basal-like cells of other organs, the human airway basal cell signature has features not previously associated with this cell type, including a unique pattern of genes encoding extracellular matrix components, G protein-coupled receptors, neuroactive ligands and receptors, and ion channels.The human airway epithelial basal cell signature identified in the present study provides novel insights into the molecular phenotype and biology of the stem/progenitor cells of the human airway epithelium.

  18. Airway Basal Cell Heterogeneity and Lung Squamous Cell Carcinoma.

    Science.gov (United States)

    Hynds, Robert E; Janes, Sam M

    2017-09-01

    Basal cells are stem/progenitor cells that maintain airway homeostasis, enact repair following epithelial injury, and are a candidate cell-of-origin for lung squamous cell carcinoma. Heterogeneity of basal cells is recognized in terms of gene expression and differentiation capacity. In this Issue, Pagano and colleagues isolate a subset of immortalized basal cells that are characterized by high motility, suggesting that they might also be heterogeneous in their biophysical properties. Motility-selected cells displayed an increased ability to colonize the lung in vivo The possible implications of these findings are discussed in terms of basal cell heterogeneity, epithelial cell migration, and modeling of metastasis that occurs early in cancer evolution. Cancer Prev Res; 10(9); 491-3. ©2017 AACR See related article by Pagano et al., p. 514 . ©2017 American Association for Cancer Research.

  19. Cognitive performance, symptoms and counter-regulation during hypoglycaemia in patients with type 1 diabetes and high or low renin-angiotensin system activity

    DEFF Research Database (Denmark)

    Høi-Hansen, Thomas; Pedersen-Bjergaard, Ulrik; Andersen, Rikke Due

    2009-01-01

    INTRODUCTION: High basal renin-angiotensin system (RAS) activity is associated with increased risk of severe hypoglycaemia in type 1 diabetes. We tested whether this might be explained by more pronounced cognitive dysfunction during hypoglycaemia in patients with high RAS activity than in patient...

  20. Bilateral hyperintense basal ganglia on T1-weighted image

    International Nuclear Information System (INIS)

    Baik, Seung Kug; Ahn, Woo Hyun; Choi, Han Yong; Kim, Bong Gi

    1994-01-01

    Bilateral high signal intensity in basal ganglia on T1-weighted images is unusual, the purpose of this study is to describe the pattern of high signal intensity and underlying disease. During the last three years, 8 patients showed bilateral high signal intensity in basal ganglia on T1-weighted image, as compared with cerebral white matter. Authors analyzed the images and underlying causes retrospectively. Of 8 patients, 5 were male and 3 were female. The age ranged from 15 days to 79 years. All patient were examined by a 0.5T superconductive MRI. Images were obtained by spin echo multislice technique. Underlying causes were 4 cases of hepatopathy, 2 cases of calcium metabolism disorder, and one case each of neurofibromatosis and hypoxic brain injury. These process were bilateral in all cases and usually symmetric. In all cases the hyperintense areas were generally homogenous without mass effect or edema, although somewhat nodular appearance was seen in neurofibromatosis. Lesions were located in the globus pallidus and internal capsule in hepatopathy and neurofibromatosis, head of the caudate nucleus in disorder of calcum metabolism, and the globus pallidus in hypoxic brain injury. Although this study is limited by its patient population, bilateral hyperintense basal ganglia is associated with various disease entities. On analysis of hyperintense basal ganglia lesion, the knowledge of clinical information improved diagnostic accuracy

  1. Meige`s syndrome associated with basal ganglia and thalamic functional disorders

    Energy Technology Data Exchange (ETDEWEB)

    Sakai, Tsutomu; Shikishima, Keigo; Kawai, Kazushige; Kitahara, Kenji [Jikei Univ., Tokyo (Japan). School of Medicine

    1998-11-01

    Magnetic resonance imaging (MRI) or single positron emission computed tomography (SPECT) or both were performed and the responses of surface electromyography (EMG) were examined in seven cases of Meige`s syndrome. MRI or SPECT or both demonstrated lesions of the basal ganglia, the thalamus, or both in five of the cases. Surface EMG revealed abnormal burst discharges in the orbicularis oculi and a failure of reciprocal muscular activity between the frontalis and orbicularis oculi in all the cases. These findings suggest that voluntary motor control and reciprocal activity in the basal ganglia-thalamocortical circuits are impaired in Meige`s syndrome. In addition, good responses were seen to clonazepam, tiapride and trihexyphenidyl in these cases. Therefore, we conclude that dopaminergic, cholinergic, and {gamma}-aminobutyric acid (GABA) ergic imbalances in the disorders of the basal ganglia and thalamus in Meige`s syndrome cause control in the excitatory and inhibitory pathways to be lost, resulting in the failure of integration in reciprocal muscular activity and voluntary motor control. This failure subsequently causes the symptoms of Meige`s syndrome. (author)

  2. External pallidal stimulation improves parkinsonian motor signs and modulates neuronal activity throughout the basal ganglia thalamic network.

    Science.gov (United States)

    Vitek, Jerrold L; Zhang, Jianyu; Hashimoto, Takao; Russo, Gary S; Baker, Kenneth B

    2012-01-01

    Deep brain stimulation (DBS) of the internal segment of the globus pallidus (GPi) and the subthalamic nucleus (STN) are effective for the treatment of advanced Parkinson's disease (PD). We have shown previously that DBS of the external segment of the globus pallidus (GPe) is associated with improvements in parkinsonian motor signs; however, the mechanism of this effect is not known. In this study, we extend our findings on the effect of STN and GPi DBS on neuronal activity in the basal ganglia thalamic network to include GPe DBS using the 1-methyl-4-phenyl-1.2.3.6-tetrahydropyridine (MPTP) monkey model. Stimulation parameters that improved bradykinesia were associated with changes in the pattern and mean discharge rate of neuronal activity in the GPi, STN, and the pallidal [ventralis lateralis pars oralis (VLo) and ventralis anterior (VA)] and cerebellar [ventralis lateralis posterior pars oralis (VPLo)] receiving areas of the motor thalamus. Population post-stimulation time histograms revealed a complex pattern of stimulation-related inhibition and excitation for the GPi and VA/VLo, with a more consistent pattern of inhibition in STN and excitation in VPLo. Mean discharge rate was reduced in the GPi and STN and increased in the VPLo. Effective GPe DBS also reduced bursting in the STN and GPi. These data support the hypothesis that therapeutic DBS activates output from the stimulated structure and changes the temporal pattern of neuronal activity throughout the basal ganglia thalamic network and provide further support for GPe as a potential therapeutic target for DBS in the treatment of PD. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Do basal Ganglia amplify willed action by stochastic resonance? A model.

    Directory of Open Access Journals (Sweden)

    V Srinivasa Chakravarthy

    Full Text Available Basal ganglia are usually attributed a role in facilitating willed action, which is found to be impaired in Parkinson's disease, a pathology of basal ganglia. We hypothesize that basal ganglia possess the machinery to amplify will signals, presumably weak, by stochastic resonance. Recently we proposed a computational model of Parkinsonian reaching, in which the contributions from basal ganglia aid the motor cortex in learning to reach. The model was cast in reinforcement learning framework. We now show that the above basal ganglia computational model has all the ingredients of stochastic resonance process. In the proposed computational model, we consider the problem of moving an arm from a rest position to a target position: the two positions correspond to two extrema of the value function. A single kick (a half-wave of sinusoid, of sufficiently low amplitude given to the system in resting position, succeeds in taking the system to the target position, with high probability, only at a critical noise level. But for suboptimal noise levels, the model arm's movements resemble Parkinsonian movement symptoms like akinetic rigidity (low noise and dyskinesias (high noise.

  4. A comparison of basal reflectivity and ice velocity in East Antarctica

    Directory of Open Access Journals (Sweden)

    R. W. Jacobel

    2010-10-01

    Full Text Available Ground-based radio echo sounding data acquired along the 1700 km US-ITASE traverse have been used to determine ice attenuation and relative basal reflectivity across the major catchments funneling ice from East Antarctica to the Ross Ice Shelf. We find that basal reflectivity varies locally by up to 40 dB which we interpret as due to changes in the phase state at the bed. Some, though not all, areas of high local reflectivity are observed to have flat-lying bed reflections indicative of sub-glacial lakes. We compare basal reflectivity to ice balance velocity and find a general association of higher flow speeds with high radar reflection strength. This set of observations from two independent remotely sensed geophysical data sets extends the range of field observations to the interior of East Antarctica and confirms the importance of basal lubrication on modulating the ice dynamics of the largest ice sheet on the planet.

  5. Heterogeneity of limbal basal epithelial progenitor cells.

    Science.gov (United States)

    Hayashida, Yasutaka; Li, Wei; Chen, Ying-Ting; He, Hua; Chen, Szu-yu; Kheirkah, Ahmad; Zhu, Ying-Tien; Matsumoto, Yukihiro; Tseng, Scheffer C G

    2010-11-01

    Although corneal epithelial stem cells (SCs) are located at the limbus between the cornea and the conjunctiva, not all limbal basal epithelial cells are SCs. Using 2 dispase digestions to remove different amounts of limbal basal epithelial cells for cross-sections, flat mounts, and cytospin preparations, double immunostaining to pancytokeratins (PCK) and vimentin (Vim) identified 3 p63+ epithelial progenitors such as PCK-/Vim+, PCK/Vim, and PCK-/Vim+ and 1 p63+ mesenchymal cell, PCK-/Vim+. PCK-/Vim- progenitors had the smallest cell size were 10-20 times more enriched on collagen I-coated dishes in the 5-minute rapid adherent fraction that contained the highest percentage of p63+ cells but the lowest percentage of cytokeratin12+ cells, and gave rise to high Ki67 labeling and vivid clonal growth. In contrast, PCK+/Vim+ and PCK+/Vim- progenitors were found more in the slow-adherent fraction and yielded poor clonal growth. PCK/Vim progenitors and clusters of PCK-/Vim+ mesenchymal cells, which were neither melanocytes nor Langerhans cells, were located in the limbal basal region. Therefore, differential expression of PCK and Vim helps identify small PCK-/Vim- cells as the most likely candidate for SCs among a hierarchy of heterogeneous limbal basal progenitors, and their close association with PCK-/Vim+ presumed "niche" cells.

  6. Identification and analysis of low molecular weight dissolved organic carbon in subglacial basal ice ecosystems by ion chromatography

    Science.gov (United States)

    Lawson, E. C.; Wadham, J. L.; Lis, G. P.; Tranter, M.; Pickard, A. E.; Stibal, M.; Dewsbury, P.; Fitzsimons, S.

    2015-08-01

    Glacial runoff is an important source of dissolved organic carbon (DOC) for downstream heterotrophic activity, despite the low overall DOC concentrations. This is because of the abundance of bioavailable, low molecular weight (LMW) DOC species. However, the provenance and character of LMW-DOC is not fully understood. We investigated the abundance and composition of DOC in subglacial environments via a molecular level DOC analysis of basal ice, which forms by water/sediment freeze-on to the glacier sole. Spectrofluorometry and a novel ion chromatographic method, which has been little utilised in glacial science for LMW-DOC determinations, were employed to identify and quantify the major LMW fractions (free amino acids, carbohydrates and carboxylic acids) in basal ice from four glaciers, each with a different basal debris type. Basal ice from Joyce Glacier (Antarctica) was unique in that 98 % of the LMW-DOC was derived from the extremely diverse FAA pool, comprising 14 FAAs. LMW-DOC concentrations in basal ice were dependent on the bioavailability of the overridden organic carbon (OC), which in turn, was influenced by the type of overridden material. Mean LMW-DOC concentrations in basal ice from Russell Glacier (Greenland), Finsterwalderbreen (Svalbard) and Engabreen (Norway) were low (0-417 nM C), attributed to the relatively refractory nature of the OC in the overridden paleosols and bedrock. In contrast, mean LMW-DOC concentrations were an order of magnitude higher (4430 nM C) in basal ice from Joyce Glacier, a reflection of the high bioavailability of the overridden lacustrine material (>17 % of the sediment OC comprised extractable carbohydrates, a proxy for bioavailable OC). We find that the overridden material may act as a direct (via abiotic leaching) and indirect (via microbial cycling) source of DOC to the subglacial environment and provides a range of LMW-DOC compounds that may stimulate microbial activity in wet sediments in current subglacial

  7. Measurement of the Effect of Phenothiazine on the Manganese Concentration in the Basal Ganglia of Sub-Human Primates by Activation Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Bird, E. D.; Grant, L. G.; Ellis, W. H. [University of Florida, Gainesville, FL (United States)

    1967-10-15

    In man toxicity to manganese and phenothiazine drugs is manifested as dyskinesia. Cotzias and co-workers demonstrated that the phenothiazines form a semiquinone radical with manganese suggesting a common mechanism for production of Parkinsonism. Previous measurements of manganese have been made on whole brain. The very sensitive technique of activation analysis was used in the present study to measure manganese concentration in various nuclei of the basal ganglia. Phenothiazine was given to one group of Rhesus monkeys (Macaca mulatta) for one month. One group served as a control. After sacrifice the basal ganglia were dissected out with plastic knives, dried, and duplicate samples exposed to thermal neutrons at a flux of 1.35 x 10{sup 12} n/cm{sup 2}s. Manganese was separated radiochemical and counts under the manganese peak were compared to a standard handled identically. The results are presented. The manganese concentration was significantly increased in the putamen of primates receiving phenothiazine. There was no significant difference in the other nuclei examined. Phenothiazine is concentrated in basal ganglia. Dopamine is found in large quantities in caudate and putamen, and following phenothiazine therapy dopamine was found to be increased slightly. The associated increase of manganese and dopamine following phenothiazine provides some evidence that this drug causes profound biochemical alterations in the basal ganglia resulting in the various dyskinesias that are seen. (author)

  8. Luminal epithelial cells within the mammary gland can produce basal cells upon oncogenic stress.

    Science.gov (United States)

    Hein, S M; Haricharan, S; Johnston, A N; Toneff, M J; Reddy, J P; Dong, J; Bu, W; Li, Y

    2016-03-17

    In the normal mammary gland, the basal epithelium is known to be bipotent and can generate either basal or luminal cells, whereas the luminal epithelium has not been demonstrated to contribute to the basal compartment in an intact and normally developed mammary gland. It is not clear whether cellular heterogeneity within a breast tumor results from transformation of bipotent basal cells or from transformation and subsequent basal conversion of the more differentiated luminal cells. Here we used a retroviral vector to express an oncogene specifically in a small number of the mammary luminal epithelial cells and tested their potential to produce basal cells during tumorigenesis. This in-vivo lineage-tracing work demonstrates that luminal cells are capable of producing basal cells on activation of either polyoma middle T antigen or ErbB2 signaling. These findings reveal the plasticity of the luminal compartment during tumorigenesis and provide an explanation for cellular heterogeneity within a cancer.

  9. A basal stem cell signature identifies aggressive prostate cancer phenotypes

    Science.gov (United States)

    Smith, Bryan A.; Sokolov, Artem; Uzunangelov, Vladislav; Baertsch, Robert; Newton, Yulia; Graim, Kiley; Mathis, Colleen; Cheng, Donghui; Stuart, Joshua M.; Witte, Owen N.

    2015-01-01

    Evidence from numerous cancers suggests that increased aggressiveness is accompanied by up-regulation of signaling pathways and acquisition of properties common to stem cells. It is unclear if different subtypes of late-stage cancer vary in stemness properties and whether or not these subtypes are transcriptionally similar to normal tissue stem cells. We report a gene signature specific for human prostate basal cells that is differentially enriched in various phenotypes of late-stage metastatic prostate cancer. We FACS-purified and transcriptionally profiled basal and luminal epithelial populations from the benign and cancerous regions of primary human prostates. High-throughput RNA sequencing showed the basal population to be defined by genes associated with stem cell signaling programs and invasiveness. Application of a 91-gene basal signature to gene expression datasets from patients with organ-confined or hormone-refractory metastatic prostate cancer revealed that metastatic small cell neuroendocrine carcinoma was molecularly more stem-like than either metastatic adenocarcinoma or organ-confined adenocarcinoma. Bioinformatic analysis of the basal cell and two human small cell gene signatures identified a set of E2F target genes common between prostate small cell neuroendocrine carcinoma and primary prostate basal cells. Taken together, our data suggest that aggressive prostate cancer shares a conserved transcriptional program with normal adult prostate basal stem cells. PMID:26460041

  10. A comparison of basal and eye-flush tears for the analysis of cat tear proteins.

    Science.gov (United States)

    Petznick, Andrea; Evans, Margaret D M; Madigan, Michele C; Markoulli, Maria; Garrett, Qian; Sweeney, Deborah F

    2011-02-01

    To identify a rapid and effective tear collection method providing sufficient tear volume and total protein content (TPC) for analysis of individual proteins in cats. Domestic adult short-haired cats (12-37 months; 2.7-6.6 kg) were used in the study. Basal tears without stimulation and eye-flush tears after instillation of saline (10 μl) were collected using microcapillary tubes from animal eyes either unwounded control or wounded with 9-mm central epithelial debridement giving four groups with n = 3. Tear comparisons were based on total time and rate for tear collection, TPC using micro bicinchoninic acid (BCA), tear immunoglobulin A (IgA), total matrix-metalloproteinase (MMP)-9 concentration using sandwich enzyme-linked immunosorbent assay (ELISA) and MMP-9 activity. Eye-flush tears were collected significantly faster than basal tears in wounded eyes with higher rates for tear collection in unwounded control and wounded eyes. TPC was significantly lower in eye-flush tears compared to basal tears. The relative proportion of tear IgA normalized to TPC (% IgA of TPC) was not significantly different between basal and eye-flush tears. In unwounded control eyes, MMP-9 was slightly higher in eye-flush than in basal tears; activity of MMP-9 in both tear types was similar. In wounded eyes, eye-flush tears showed highest MMP-9 levels and activity on Day 1, which subsequently decreased to Day 7. MMP-9 activity in basal tears from wounded eyes did not display changes in expression. Eye-flush tears can be collected rapidly providing sufficient tear volume and TPC. This study also indicates that eye-flush tears may be more suitable than basal tears for the analysis of MMPs following corneal wounding. © 2011 The Authors. Acta Ophthalmologica © 2011 Acta Ophthalmologica Scandinavica Foundation.

  11. Molecular mechanisms in the selective basal activation of pyrabactin receptor 1: Comparative analysis of mutants.

    Science.gov (United States)

    Dorosh, Lyudmyla; Rajagopalan, Nandhakishore; Loewen, Michele C; Stepanova, Maria

    2014-01-01

    Pyrabactin receptors (PYR) play a central role in abscisic acid (ABA) signal transduction; they are ABA receptors that inhibit type 2C protein phosphatases (PP2C). Molecular aspects contributing to increased basal activity of PYR against PP2C are studied by molecular dynamics (MD) simulations. An extensive series of MD simulations of the apo-form of mutagenized PYR1 as a homodimer and in complex with homology to ABA-insensitive 1 (HAB1) phosphatase are reported. In order to investigate the detailed molecular mechanisms mediating PYR1 activity, the MD data was analyzed by essential collective dynamics (ECD), a novel approach that allows the identification, with atomic resolution, of persistent dynamic correlations based on relatively short MD trajectories. Employing the ECD method, the effects of select mutations on the structure and dynamics of the PYR1 complexes were investigated and considered in the context of experimentally determined constitutive activities against HAB1. Approaches to rationally design constitutively active PYR1 constructs to increase PP2C inhibition are discussed.

  12. Review and analysis of management guidelines of basal cell carcinoma

    International Nuclear Information System (INIS)

    Garcia Nunez, Hernan

    2013-01-01

    International guidelines for management of basal cell carcinoma are reviewed and analyzed for decision-making in the appropriate therapeutic behavior for patients. The different therapies for the treatment of basal cell carcinoma are described. Different therapies are evaluated according to the risk (low or high) of recurrence to determine the appropriate treatment. According to the evidence, low-risk tumors have responded to topical therapy, curettage and electrodesiccation, cryotherapy or simple resection, and high-risk tumors are managed with surgery, radiotherapy or Mohs' micrographic surgery [es

  13. Polychlorinated biphenyl 126 stimulates basal and inducible aldosterone biosynthesis of human adrenocortical H295R cells

    International Nuclear Information System (INIS)

    Li, L.-A.; Wang, P.-W.; Chang, Louis W.

    2004-01-01

    To understand the effects of polychlorinated biphenyls (PCBs) on adrenal aldosterone biosynthesis, we have performed a systematical study to characterize the corresponding steroidogenic response of human adrenocortical cell line H295R to PCB126 exposure. We found that PCB126 at high concentrations stimulated basal and inducible aldosterone production. The aldosterone induction occurred concomitantly with activation of the CYP11B2 gene. Despite the fact that PCB126 acted in synergy with both potassium and angiotensin II (Ang II) in activation of aldosterone synthesis, PCB126 only modestly increased CYP11B2 mRNA expression in the presence of Ang II contrary to the synergistic transcriptional induction elicited by PCB126 and potassium. This implicated that PCB126 had differential interactions with the potassium and Ang II signaling systems in the regulation of aldosterone biosynthesis. In addition, high concentrations of PCB126 elevated transcriptional expression of the type I Ang II receptor (AT 1 ) and might thus sensitize the cellular Ang II responsiveness in both basal and inducible aldosterone biosynthesis. SF-1 was not involved in the PCB126-induced transcriptional regulation despite its importance in steroidogenic gene activation

  14. Future of newer basal insulin

    OpenAIRE

    Madhu, S. V.; Velmurugan, M.

    2013-01-01

    Basal insulin have been developed over the years. In recent times newer analogues have been added to the armanentarium for diabetes therapy. This review specifically reviews the current status of different basal insulins

  15. Computational modelling of locomotor muscle moment arms in the basal dinosaur Lesothosaurus diagnosticus: assessing convergence between birds and basal ornithischians.

    Science.gov (United States)

    Bates, Karl T; Maidment, Susannah C R; Allen, Vivian; Barrett, Paul M

    2012-03-01

    Ornithischia (the 'bird-hipped' dinosaurs) encompasses bipedal, facultative quadrupedal and quadrupedal taxa. Primitive ornithischians were small bipeds, but large body size and obligate quadrupedality evolved independently in all major ornithischian lineages. Numerous pelvic and hind limb features distinguish ornithischians from the majority of other non-avian dinosaurs. However, some of these features, notably a retroverted pubis and elongate iliac preacetabular process, appeared convergently in maniraptoran theropods, and were inherited by their avian descendants. During maniraptoran/avian evolution these pelvic modifications led to significant changes in the functions of associated muscles, involving alterations to the moment arms and the activation patterns of pelvic musculature. However, the functions of these features in ornithischians and their influence on locomotion have not been tested and remain poorly understood. Here, we provide quantitative tests of bipedal ornithischian muscle function using computational modelling to estimate 3D hind limb moment arms for the most complete basal ornithischian, Lesothosaurus diagnosticus. This approach enables sensitivity analyses to be carried out to explore the effects of uncertainties in muscle reconstructions of extinct taxa, and allows direct comparisons to be made with similarly constructed models of other bipedal dinosaurs. This analysis supports some previously proposed qualitative inferences of muscle function in basal ornithischians. However, more importantly, this work highlights ambiguities in the roles of certain muscles, notably those inserting close to the hip joint. Comparative analysis reveals that moment arm polarities and magnitudes in Lesothosaurus, basal tetanuran theropods and the extant ostrich are generally similar. However, several key differences are identified, most significantly in comparisons between the moment arms of muscles associated with convergent osteological features in

  16. Effects of high-frequency stimulation of the internal pallidal segment on neuronal activity in the thalamus in parkinsonian monkeys

    OpenAIRE

    Kammermeier, Stefan; Pittard, Damien; Hamada, Ikuma; Wichmann, Thomas

    2016-01-01

    It is known that parkinsonism is associated with abnormalities in basal ganglia activity and that deep brain stimulation of these structures, a common treatment for Parkinson's disease, strongly alters basal ganglia output. However, parkinsonism- and stimulation-related activity changes in the ventral thalamus, a major recipient of basal ganglia output, remain controversial. These primate experiments demonstrate such changes, emphasizing emerging oscillatory activity patterns, and changes of ...

  17. Vulvar basal cell carcinoma, a rare location

    Directory of Open Access Journals (Sweden)

    Cornelia Nitipir

    2018-05-01

    Full Text Available Basal Cell Carcinoma is the most common human malignant neoplasm. Vulvar basal cell carcinoma is rare, accounting for less than 5% of all vulvar neoplasms. Vulvar basal cell carcinomas are usually diagnosed late because they are often asymptomatic and tend to grow at slow rates. They are usually diagnosed late because they are often asymptomatic. However, these tumours may appear in areas which are normally covered with ultraviolet light. We present the case of a 60 years old woman diagnosed with invasive breast cancer for which she underwent surgery followed by chemotherapy and radiotherapy. The patient presented to our department with an ulcerated vulvar lesion. On inspection, the tumour measured 3/2 cm and was located on the left labium majus. The biopsy confirmed the diagnosis of vulvar basal cell carcinoma and a wide local excision was performed with no relapse at one year. In conclusion, early detection of BCC’s is critical to allow complete surgical cure so any abnormality on the vulva should be biopsied. A wide safety margin of 1cm should be achieved when resecting the tumour and the physician should keep in mind that the BCC’s of the vulva has a high recurrence rate. Previous chemotherapy is not associated with this type of non-melanoma skin cancer.

  18. Basal cell carcinoma-treatment with cryosurgery

    Directory of Open Access Journals (Sweden)

    Kaur S

    2003-03-01

    Full Text Available Basal cell carcinoma is a common cutaneous malignancy, frequently occurring over the face in elderly individuals. Various therapeutic modalities are available to treat these tumors. We describe three patients with basal cell carcinoma successfully treated with cryosurgery and discuss the indications and the use of this treatment modality for basal cell carcinomas.

  19. Metastatic giant basal cell carcinoma: a case report.

    Science.gov (United States)

    Bellahammou, Khadija; Lakhdissi, Asmaa; Akkar, Othman; Rais, Fadoua; Naoual, Benhmidou; Elghissassi, Ibrahim; M'rabti, Hind; Errihani, Hassan

    2016-01-01

    Basal cell carcinoma is the most common skin cancer, characterised by a slow growing behavior, metastasis are extremely rare, and it occurs in less than 0, 1% of all cases. Giant basal cell carcinoma is a rare form of basal cell carcinoma, more aggressive and defined as a tumor measuring more than 5 cm at its largest diameter. Only 1% of all basal cell carcinoma develops to a giant basal cell carcinoma, resulting of patient's negligence. Giant basal cell carcinoma is associated with higher potential of metastasis and even death, compared to ordinary basal cell carcinoma. We report a case of giant basal cell carcinoma metastaticin lung occurring in a 79 years old male patient, with a fatal evolution after one course of systemic chemotherapy. Giant basal cell carcinoma is a very rare entity, early detection of these tumors could prevent metastasis occurrence and improve the prognosis of this malignancy.

  20. Probing the Surface Charge on the Basal Planes of Kaolinite Particles with High-Resolution Atomic Force Microscopy.

    Science.gov (United States)

    Kumar, N; Andersson, M P; van den Ende, D; Mugele, F; Siretanu, I

    2017-12-19

    High-resolution atomic force microscopy is used to map the surface charge on the basal planes of kaolinite nanoparticles in an ambient solution of variable pH and NaCl or CaCl 2 concentration. Using DLVO theory with charge regulation, we determine from the measured force-distance curves the surface charge distribution on both the silica-like and the gibbsite-like basal plane of the kaolinite particles. We observe that both basal planes do carry charge that varies with pH and salt concentration. The silica facet was found to be negatively charged at pH 4 and above, whereas the gibbsite facet is positively charged at pH below 7 and negatively charged at pH above 7. Investigations in CaCl 2 at pH 6 show that the surface charge on the gibbsite facet increases for concentration up to 10 mM CaCl 2 and starts to decrease upon further increasing the salt concentration to 50 mM. The increase of surface charge at low concentration is explained by Ca 2+ ion adsorption, while Cl - adsorption at higher CaCl 2 concentrations partially neutralizes the surface charge. Atomic resolution imaging and density functional theory calculations corroborate these observations. They show that hydrated Ca 2+ ions can spontaneously adsorb on the gibbsite facet of the kaolinite particle and form ordered surface structures, while at higher concentrations Cl - ions will co-adsorb, thereby changing the observed ordered surface structure.

  1. The Wnt receptor, Lrp5, is expressed by mouse mammary stem cells and is required to maintain the basal lineage.

    Directory of Open Access Journals (Sweden)

    Nisha M Badders

    2009-08-01

    Full Text Available Ectopic Wnt signaling induces increased stem/progenitor cell activity in the mouse mammary gland, followed by tumor development. The Wnt signaling receptors, Lrp5/6, are uniquely required for canonical Wnt activity. Previous data has shown that the absence of Lrp5 confers resistance to Wnt1-induced tumor development.Here, we show that all basal mammary cells express Lrp5, and co-express Lrp6 in a similar fashion. Though Wnt dependent transcription of key target genes is relatively unchanged in mammary epithelial cell cultures, the absence of Lrp5 specifically depletes adult regenerative stem cell activity (to less than 1%. Stem cell activity can be enriched by >200 fold (over 80% of activity, based on high Lrp5 expression alone. Though Lrp5 null glands have apparent normal function, the basal lineage is relatively reduced (from 42% basal/total epithelial cells to 22% and Lrp5-/- mammary epithelial cells show enhanced expression of senescence-associated markers in vitro, as measured by expression of p16(Ink4a and TA-p63.This is the first single biomarker that has been demonstrated to be functionally involved in stem cell maintenance. Together, these results demonstrate that Wnt signaling through Lrp5 is an important component of normal mammary stem cell function.

  2. The role of inhibition in generating and controlling Parkinson's disease oscillations in the basal ganglia

    Directory of Open Access Journals (Sweden)

    Arvind eKumar

    2011-10-01

    Full Text Available Movement disorders in Parkinson's disease (PD are commonly associated with slow oscillations and increased synchrony of neuronal activity in the basal ganglia. The neural mechanisms underlying this dynamic network dysfunction, however, are only poorly understood. Here, we show that the strength of inhibitory inputs from striatum to globus pallidus external (GPe is a key parameter controlling oscillations in the basal ganglia. Specifically, the increase in striatal activity observed in PD is sufficient to unleash the oscillations in the basal ganglia. This finding allows us to propose a unified explanation for different phenomena: absence of oscillation in the healthy state of the basal ganglia, oscillations in dopamine-depleted state and quenching of oscillations under deep brain stimulation (DBS. These novel insights help us to better understand and optimize the function of DBS protocols. Furthermore, studying the model behaviour under transient increase of activity of the striatal neurons projecting to the indirect pathway, we are able to account for both motor impairment in PD patients and for reduced response inhibition in DBS implanted patients.

  3. Opponent and bidirectional control of movement velocity in the basal ganglia

    Science.gov (United States)

    Yttri, Eric A.

    2016-01-01

    For goal-directed behavior it is critical that we can both select the appropriate action and learn to modify the underlying movements (e.g. the pitch of a note or velocity of a reach) to improve outcomes. The basal ganglia are a critical nexus where circuits necessary for the production of behavior, such as neocortex and thalamus, are integrated with reward signaling 1 to reinforce successful, purposive actions 2. Dorsal striatum, a major input structure of basal ganglia is composed of two opponent pathways, direct and indirect, thought to select actions that elicit positive outcomes or suppress actions that do not, respectively 3,4. Activity-dependent plasticity modulated by reward is thought to be sufficient for selecting actions in striatum 5,6. Although perturbations of basal ganglia function produce profound changes in movement 7, it remains unknown whether activity-dependent plasticity is sufficient to produce learned changes in movement kinematics, such as velocity. Here we used cell-type specific stimulation delivered in closed-loop during movement to demonstrate that activity in either the direct or indirect pathway is sufficient to produce specific and sustained increases or decreases in velocity without affecting action selection or motivation. These behavioral changes were a form of learning that accumulated over trials, persisted after the cessation of stimulation, and were abolished in the presence of dopamine antagonists. Our results reveal that the direct and indirect pathways can each bidirectionally control movement velocity, demonstrating unprecedented specificity and flexibility in the control of volition by the basal ganglia. PMID:27135927

  4. Basal ganglia modulation of thalamocortical relay in Parkinson's disease and dystonia.

    Science.gov (United States)

    Guo, Yixin; Park, Choongseok; Worth, Robert M; Rubchinsky, Leonid L

    2013-01-01

    Basal ganglia dysfunction has being implied in both Parkinson's disease and dystonia. While these disorders probably involve different cellular and circuit pathologies within and beyond basal ganglia, there may be some shared neurophysiological pathways. For example, pallidotomy and pallidal Deep Brain Stimulation (DBS) are used in symptomatic treatment of both disorders. Both conditions are marked by alterations of rhythmicity of neural activity throughout basal ganglia-thalamocortical circuits. Increased synchronized oscillatory activity in beta band is characteristic of Parkinson's disease, while different frequency bands, theta and alpha, are involved in dystonia. We compare the effect of the activity of GPi, the output nuclei of the basal ganglia, on information processing in the downstream neural circuits of thalamus in Parkinson's disease and dystonia. We use a data-driven computational approach, a computational model of the thalamocortical (TC) cell modulated by experimentally recorded data, to study the differences and similarities of thalamic dynamics in dystonia and Parkinson's disease. Our analysis shows no substantial differences in TC relay between the two conditions. Our results suggest that, similar to Parkinson's disease, a disruption of thalamic processing could also be involved in dystonia. Moreover, the degree to which TC relay fidelity is impaired is approximately the same in both conditions. While Parkinson's disease and dystonia may have different pathologies and differ in the oscillatory content of neural discharge, our results suggest that the effect of patterning of pallidal discharge is similar in both conditions. Furthermore, these results suggest that the mechanisms of GPi DBS in dystonia may involve improvement of TC relay fidelity.

  5. Effect of 3-Day Bed Rest on the Basal Sympathetic Activity and Responsiveness of this System to Physiological Stimuli In Athletes and Sedentary Subjects

    Science.gov (United States)

    Smorawinski, Jerzy; Adrian, Jacek; Kaciuba-Uscilko, Hanna; Nazar, Krystyna; Greenleaf, John E.; Dalton, P. Bonnie (Technical Monitor)

    2002-01-01

    The aims of this study were: (1) to examine the effect of three days of bed rest (BR) on basal plasma epinephrine [E] and norepinephrine [NE] and the catecholamine responses to various physiological stimuli, and (2) to find out whether previous physical activity modifies effects of BR. In the first series, 29 young men (11 sedentary students, 8 endurance and 10 strength trained athletes) were submitted to oral glucose tolerance test in supine position and to active orthostatic test before and after 3 days of BR. Plasma [E] and [NE] were measured after overnight fast (basal condition), at 60, 120 and 180 min after glucose ingestion (70 a), and at the 8th min of unsupported standing. In the second series, other 22 subjects (12 sedentary students, 10 endurance and 10 strength trained athletes) were submitted to 2 min cold pressor test (CPT) and exercise. Plasma E and NE were determined in the supine position after overnight fast and at 60th and 120th s of hand cooling. Then, after breakfast followed by 2-3 hour sitting, the subjects performed cycle ergometer exercise with workload increasing until volitional exhaustion. Plasma [E] and [NE] were determined at the end of each load. Plasma catecholamines were determined made radioenzymatically. After BR, basal plasma [NE] was decreased in endurance and strength athletes (psedentary subjects. In neither group BR affected the basal [E]. Responses of both catecholamines to glucose load were diminished after BR in all three groups (pwork intensity after than before BR (p<0.05).

  6. Two cases of seborrheic keratosis with basal clear cells.

    Science.gov (United States)

    Anan, Takashi; Fukumoto, Takaya; Kimura, Tetsunori

    2017-03-01

    Seborrheic keratosis with basal clear cells (SKBCC) is an extremely rare histopathological variant of seborrheic keratosis that has histological similarities to melanoma in situ. We herein report two cases of SKBCC and provide the first description of the dermoscopic features of this condition, in addition to the histopathological findings. Both of the two lesions showed typical histological architectures of seborrheic keratosis with rows or focal clusters of monomorphic clear cells with abundant pale cytoplasm and small round nucleus in the basal layer. Immunohistochemical examination revealed that most clear cells were positive for high molecular weight cytokeratin (34βE12) in a peripheral pattern but were negative tor Melan-A. Dermoscopy revealed typical features of ordinary seborrheic keratosis, while unfortunately did not reflect the presence of basal clear cells. © 2016 Japanese Dermatological Association.

  7. Computed tomography of granulomatous basal meningitis caused by pneumococcus

    Energy Technology Data Exchange (ETDEWEB)

    Sonobe, Makoto; Takahashi, Shinichiro (Mito National Hospital, Ibaraki (Japan)); Ohara, Kazuo

    1983-07-01

    A case of 3-month-old female with ''granulomatous basal meningitis'' caused by pneumococcus was described. She suffered from high fever, vomiting, convulsion and loss of consciousness on January 28th, 1982. On admission the protein content of the spinal fluid was 280 mg/100 ml, the glucose 4 mg/100 ml and the cell count was 1206/3(L : 845, N : 361). Her symptoms and signs were deteriorated in spite of antibiotics and anticonvulsants. CT scan on the 10th day showed the enhanced basal cistern. She died on the 11th day but autopsy was not carried out. In this case, pneumococcus was cultured in CSF. This seemed to be the first case of ''granulomatous basal meningitis'' due to purulent meningitis in Japan.

  8. Electrochemical maps and movies of the hydrogen evolution reaction on natural crystals of molybdenite (MoS2): basal vs. edge plane activity.

    Science.gov (United States)

    Bentley, Cameron L; Kang, Minkyung; Maddar, Faduma M; Li, Fengwang; Walker, Marc; Zhang, Jie; Unwin, Patrick R

    2017-09-01

    Two dimensional (2D) semiconductor materials, such as molybdenum disulfide (MoS 2 ) have attracted considerable interest in a range of chemical and electrochemical applications, for example, as an abundant and low-cost alternative electrocatalyst to platinum for the hydrogen evolution reaction (HER). While it has been proposed that the edge plane of MoS 2 possesses high catalytic activity for the HER relative to the "catalytically inert" basal plane, this conclusion has been drawn mainly from macroscale electrochemical (voltammetric) measurements, which reflect the "average" electrocatalytic behavior of complex electrode ensembles. In this work, we report the first spatially-resolved measurements of HER activity on natural crystals of molybdenite, achieved using voltammetric scanning electrochemical cell microscopy (SECCM), whereby pixel-resolved linear-sweep voltammogram (LSV) measurements have allowed the HER to be visualized at multiple different potentials to construct electrochemical flux movies with nanoscale resolution. Key features of the SECCM technique are that characteristic surface sites can be targeted and analyzed in detail and, further, that the electrocatalyst area is known with good precision (in contrast to many macroscale measurements on supported catalysts). Through correlation of the local voltammetric response with information from scanning electron microscopy (SEM) and atomic force microscopy (AFM) in a multi-microscopy approach , it is demonstrated unequivocally that while the basal plane of bulk MoS 2 (2H crystal phase) possesses significant activity, the HER is greatly facilitated at the edge plane ( e.g. , surface defects such as steps, edges or crevices). Semi-quantitative treatment of the voltammetric data reveals that the HER at the basal plane of MoS 2 has a Tafel slope and exchange current density ( J 0 ) of ∼120 mV per decade and 2.5 × 10 -6 A cm -2 (comparable to polycrystalline Co, Ni, Cu and Au), respectively, while the edge

  9. Photodynamic therapy for basal cell carcinoma.

    Science.gov (United States)

    Fargnoli, Maria Concetta; Peris, Ketty

    2015-11-01

    Topical photodynamic therapy is an effective and safe noninvasive treatment for low-risk basal cell carcinoma, with the advantage of an excellent cosmetic outcome. Efficacy of photodynamic therapy in basal cell carcinoma is supported by substantial research and clinical trials. In this article, we review the procedure, indications and clinical evidences for the use of photodynamic therapy in the treatment of basal cell carcinoma.

  10. Uniformity in the basal metabolic rate of marsupials: its causes and consequences Uniformidad en la tasa metabólica basal de marsupiales: sus causas y consecuencias

    Directory of Open Access Journals (Sweden)

    BRIAN K. MACNAB

    2005-06-01

    Full Text Available Most of the variation (98.8 % in basal rate of metabolism (BMR in 70 species of marsupials is correlated with body mass, although lowland species have higher basal rates than highland species and burrowers have lower basal rates than non-burrowers. These factors collectively account for 99.2 % of the variation in marsupial BMR. Marsupials differ in BMR from eutherians by having no species with a high basal rate by general mammalian standards, even when consuming vertebrates or grass, food habits that are associated with very high basal rates in eutherians. The absence of high basal rates in marsupials reflects the absence of a correlation of rate of reproduction with basal rate, a correlation present in eutherians. These differences have two consequences: (1 marsupials are less tolerant of cold environments than eutherians, and (2 marsupials coexist with eutherians only when both have food habits associated with low basal rates and therefore when eutherians have reduced rates of reproduction. In Australia and South America marsupial carnivores diversified in the absence of eutherian equivalents. The importation to mainland Australia of dingos by humans appears to have been the immediate cause for the extinction of thylacines, Tasmanian devils, and eastern quolls. Carnivorous marsupials in South America were replaced by eutherians with the completion of the Panamanian land bridge. Macropods, which have lower basal rates than eutherian grazers, survive in central Australia probably because of their adjustment to xeric environments, whereas introduced domestic stock require the provision of water by humansGran parte de la variación (98,5 en la tasa metabólica basal de 70 especies de marsupiales se correlaciona con la masa corporal, aunque las especies de tierras bajas tienes tasas basales mayores que las de tierras altas, y las especies subterráneas tienes BMR’s menores que las no subterráneas. Colectivamente, estos factores dan cuenta de un

  11. Red Dot Basal Cell Carcinoma: Report of Cases and Review of This Unique Presentation of Basal Cell Carcinoma.

    Science.gov (United States)

    Cohen, Philip R

    2017-03-22

    Red dot basal cell carcinoma is a unique variant of basal cell carcinoma. Including the three patients described in this report, red dot basal cell carcinoma has only been described in seven individuals. This paper describes the features of two males and one female with red dot basal cell carcinoma and reviews the characteristics of other patients with this clinical subtype of basal cell carcinoma. A 70-year-old male developed a pearly-colored papule with a red dot in the center on his nasal tip. A 71-year-old male developed a red dot surrounded by a flesh-colored papule on his left nostril. Lastly, a 74-year-old female developed a red dot within an area of erythema on her left mid back. Biopsy of the lesions all showed nodular and/or superficial basal cell carcinoma. Correlation of the clinical presentation and pathology established the diagnosis of red dot basal cell carcinoma. The tumors were treated by excision using the Mohs surgical technique. Pubmed was searched with the keyword: basal, cell, cancer, carcinoma, dot, red, and skin. The papers generated by the search and their references were reviewed. Red dot basal cell carcinoma has been described in three females and two males; the gender was not reported in two patients. The tumor was located on the nose (five patients), back (one patient) and thigh (one patient). Cancer presented as a solitary small red macule or papule; often, the carcinoma was surrounded by erythema or a flesh-colored papule. Although basal cell carcinomas usually do not blanch after a glass microscope slide is pressed against them, the red dot basal cell carcinoma blanched after diascopy in two of the patients, resulting in a delay of diagnosis in one of these individuals. Dermoscopy may be a useful non-invasive modality for evaluating skin lesions when the diagnosis of red dot basal cell carcinoma is considered. Mohs surgery is the treatment of choice; in some of the patients, the ratio of the area of the postoperative wound to that

  12. Positron emission tomography and basal ganglia functions

    International Nuclear Information System (INIS)

    Kato, Motohiro; Otsuka, Makoto; Taniwaki, Koukyo; Hosokawa, Shinichi; Kuwabara, Yasuo; Ichiya, Yuichi

    1990-01-01

    With the advent of positron emission tomography (PET), studies on the human brain function and pathophysiology of brain damage have been extremely progressed. It is well-known that the basal ganglia plays an important role as one of the central nervous system involved in exercise regulation. More recently, the potential involvement of the basal ganglia in psychological processes, such as cognitive function, has been pointed out, receiving much attention. In spite of such a lot of studies, however, basal ganglia function remains unclear. This paper describes the relationships between PET findings and basal ganglia function. PET findings are discussed in relation to brain energy metabolism and striatal dopamine function. Pathophysiology of the basal ganglia are described in terms of the following diseases: Parkinson's disease, Parkinson's syndrome, progressive supranuclear palsy, Huntington's disease, and dystonia. Physiological backgrounds of the basal ganglia for PET images are also referred to. (N.K.) 75 refs

  13. Positron emission tomography and basal ganglia functions

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Motohiro; Otsuka, Makoto; Taniwaki, Koukyo; Hosokawa, Shinichi; Kuwabara, Yasuo; Ichiya, Yuichi [Kyushu Univ., Fukuoka (Japan). Faculty of Medicine

    1990-05-01

    With the advent of positron emission tomography (PET), studies on the human brain function and pathophysiology of brain damage have been extremely progressed. It is well-known that the basal ganglia plays an important role as one of the central nervous system involved in exercise regulation. More recently, the potential involvement of the basal ganglia in psychological processes, such as cognitive function, has been pointed out, receiving much attention. In spite of such a lot of studies, however, basal ganglia function remains unclear. This paper describes the relationships between PET findings and basal ganglia function. PET findings are discussed in relation to brain energy metabolism and striatal dopamine function. Pathophysiology of the basal ganglia are described in terms of the following diseases: Parkinson's disease, Parkinson's syndrome, progressive supranuclear palsy, Huntington's disease, and dystonia. Physiological backgrounds of the basal ganglia for PET images are also referred to. (N.K.) 75 refs.

  14. ATP-dependent calcium transport across basal plasma membranes of human placental trophoblast

    International Nuclear Information System (INIS)

    Fisher, G.J.; Kelley, L.K.; Smith, C.H.

    1987-01-01

    As a first step in understanding the cellular basis of maternal-fetal calcium transfer, the authors examined the characteristics of calcium uptake by a highly purified preparation of the syncytiotrophoblast basal (fetal facing) plasma membrane. In the presence of nanomolar concentrations of free calcium, basal membranes demonstrated substantial ATP-dependent calcium uptake. This uptake required magnesium, was not significantly affected by Na + or K + (50 mM), or sodium azide (10 mM). Intravesicular calcium was rapidly and completely released by the calcium ionophore rapidly and completely released by the calcium ionophore A23187. Calcium transport was significantly stimulated by the calcium-dependent regulatory protein calmodulin. Placental membrane fractions enriched in endoplasmic reticulum (ER) and mitochondria also demonstrated ATP-dependent calcium uptake. In contrast to basal membrane, mitochondrial calcium uptake was completely inhibited by azide. The rate of calcium uptake was completely inhibited by azide. The rate of calcium uptake by the ER was only 20% of that of basal membranes. They conclude that the placental basal plasma membrane possesses a high-affinity calcium transport system similar to that found in plasma membranes of a variety of cell types. This transporter is situated to permit it to function in vivo in maternal-fetal calcium transfer

  15. Ezh2 represses the basal cell lineage during lung endoderm development.

    Science.gov (United States)

    Snitow, Melinda E; Li, Shanru; Morley, Michael P; Rathi, Komal; Lu, Min Min; Kadzik, Rachel S; Stewart, Kathleen M; Morrisey, Edward E

    2015-01-01

    The development of the lung epithelium is regulated in a stepwise fashion to generate numerous differentiated and stem cell lineages in the adult lung. How these different lineages are generated in a spatially and temporally restricted fashion remains poorly understood, although epigenetic regulation probably plays an important role. We show that the Polycomb repressive complex 2 component Ezh2 is highly expressed in early lung development but is gradually downregulated by late gestation. Deletion of Ezh2 in early lung endoderm progenitors leads to the ectopic and premature appearance of Trp63+ basal cells that extend the entire length of the airway. Loss of Ezh2 also leads to reduced secretory cell differentiation. In their place, morphologically similar cells develop that express a subset of basal cell genes, including keratin 5, but no longer express high levels of either Trp63 or of standard secretory cell markers. This suggests that Ezh2 regulates the phenotypic switch between basal cells and secretory cells. Together, these findings show that Ezh2 restricts the basal cell lineage during normal lung endoderm development to allow the proper patterning of epithelial lineages during lung formation. © 2015. Published by The Company of Biologists Ltd.

  16. Impact of Basal Conditions on Grounding-Line Retreat

    Science.gov (United States)

    Koellner, S. J.; Parizek, B. R.; Alley, R. B.; Muto, A.; Holschuh, N.; Nowicki, S.

    2017-12-01

    An often-made assumption included in ice-sheet models used for sea-level projections is that basal rheology is constant throughout the domain of the simulation. The justification in support of this assumption is that physical data for determining basal rheology is limited and a constant basal flow law can adequately approximate current as well as past behavior of an ice-sheet. Prior studies indicate that beneath Thwaites Glacier (TG) there is a ridge-and-valley bedrock structure which likely promotes deformation of soft tills within the troughs and sliding, more akin to creep, over the harder peaks; giving rise to a spatially variable basal flow law. Furthermore, it has been shown that the stability of an outlet glacier varies with the assumed basal rheology, so accurate projections almost certainly need to account for basal conditions. To test the impact of basal conditions on grounding-line evolution forced by ice-shelf perturbations, we modified the PSU 2-D flowline model to enable the inclusion of spatially variable basal rheology along an idealized bedrock profile akin to TG. Synthetic outlet glacier "data" were first generated under steady-state conditions assuming a constant basal flow law and a constant basal friction coefficient field on either a linear or bumpy sloping bed. In following standard procedures, a suite of models were then initialized by assuming different basal rheologies and then determining the basal friction coefficients that produce surface velocities matching those from the synthetic "data". After running each of these to steady state, the standard and full suite of models were forced by drastically reducing ice-shelf buttressing through side-shear and prescribed basal-melting perturbations. In agreement with previous findings, results suggest a more plastic basal flow law enhances stability in response to ice-shelf perturbations by flushing ice from farther upstream to sustain the grounding-zone mass balance required to prolong the

  17. Endothelial MMP14 is required for endothelial-dependent growth support of human airway basal cells

    Science.gov (United States)

    Ding, Bi-Sen; Gomi, Kazunori; Rafii, Shahin; Crystal, Ronald G.; Walters, Matthew S.

    2015-01-01

    ABSTRACT Human airway basal cells are the stem (or progenitor) population of the airway epithelium, and play a central role in anchoring the epithelium to the basement membrane. The anatomic position of basal cells allows for potential paracrine signaling between them and the underlying non-epithelial stromal cells. In support of this, we have previously demonstrated that endothelial cells support growth of basal cells during co-culture through vascular endothelial growth factor A (VEGFA)-mediated signaling. Building on these findings, we found, by RNA sequencing analysis, that basal cells expressed multiple fibroblast growth factor (FGF) ligands (FGF2, FGF5, FGF11 and FGF13) and that only FGF2 and FGF5 were capable of functioning in a paracrine manner to activate classical FGF receptor (FGFR) signaling. Antibody-mediated blocking of FGFR1 during basal-cell–endothelial-cell co-culture significantly reduced the endothelial-cell-dependent basal cell growth. Stimulation of endothelial cells with basal-cell-derived growth factors induced endothelial cell expression of matrix metallopeptidase 14 (MMP14), and short hairpin RNA (shRNA)-mediated knockdown of endothelial cell MMP14 significantly reduced the endothelial-cell-dependent growth of basal cells. Overall, these data characterize a new growth-factor-mediated reciprocal ‘crosstalk’ between human airway basal cells and endothelial cells that regulates proliferation of basal cells. PMID:26116571

  18. Basal-body-associated macromolecules: a continuing debate.

    Science.gov (United States)

    Pierre Mignot, J; Brugerolle, G; Didier, P; Bornens, M

    1993-07-01

    Controversy over the possibility that centrioles/basal bodies contain nucleic acids has overshadowed results demonstrating other macromolecules in the lumen of these organelles. Glycogen particles, which are known to be present within the lumen of the centriole/basal body of sperm cells, have now been found in basal bodies of protists belonging to three different groups. Here, we extend the debate on a role for RNA in basal body/centriole function and speculate on the origin and the function of centriolar glycogen.

  19. Effect of diet on maintenance of acid-basal balance in blood of dairy cows

    Directory of Open Access Journals (Sweden)

    Gaál T.

    2003-01-01

    Full Text Available High-performance breeds of ruminants often exhibit production disorders which can be accompanied by a disturbed acid-basal balance. Most of the disorders in the acid-basal balance are closely related to digressions in the diet norms of these animals. A deficiency or surplus of energy equally cause disorders in the acid-basal status of the organism. Metabolic acidosis is the most frequent of the four types of basic disorders in the acid-basal balance in ruminants. It appears as a consequence of rumen acidosis, ketosis, or diarrhea. Acute disorders in the acid-basal balance are far more dangerous than chronic ones. Therapy of the basic diseases is generally sufficient compensation for the effects of the acid-basal disorders, but in certain cases it is necessary to perform alkalization, that is, acidification of the rumen content using the necessary preparations.

  20. The G protein Gi1 exhibits basal coupling but not preassembly with G protein-coupled receptors.

    Science.gov (United States)

    Bondar, Alexey; Lazar, Josef

    2017-06-09

    The G i/o protein family transduces signals from a diverse group of G protein-coupled receptors (GPCRs). The observed specificity of G i/o -GPCR coupling and the high rate of G i/o signal transduction have been hypothesized to be enabled by the existence of stable associates between G i/o proteins and their cognate GPCRs in the inactive state (G i/o -GPCR preassembly). To test this hypothesis, we applied the recently developed technique of two-photon polarization microscopy (2PPM) to Gα i1 subunits labeled with fluorescent proteins and four GPCRs: the α 2A -adrenergic receptor, GABA B , cannabinoid receptor type 1 (CB 1 R), and dopamine receptor type 2. Our experiments with non-dissociating mutants of fluorescently labeled Gα i1 subunits (exhibiting impaired dissociation from activated GPCRs) showed that 2PPM is capable of detecting GPCR-G protein interactions. 2PPM experiments with non-mutated fluorescently labeled Gα i1 subunits and α 2A -adrenergic receptor, GABA B , or dopamine receptor type 2 receptors did not reveal any interaction between the G i1 protein and the non-stimulated GPCRs. In contrast, non-stimulated CB 1 R exhibited an interaction with the G i1 protein. Further experiments revealed that this interaction is caused solely by CB 1 R basal activity; no preassembly between CB 1 R and the G i1 protein could be observed. Our results demonstrate that four diverse GPCRs do not preassemble with non-active G i1 However, we also show that basal GPCR activity allows interactions between non-stimulated GPCRs and G i1 (basal coupling). These findings suggest that G i1 interacts only with active GPCRs and that the well known high speed of GPCR signal transduction does not require preassembly between G proteins and GPCRs. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. Report Card on Basal Readers.

    Science.gov (United States)

    Goodman, Kenneth S.; And Others

    This report examines the nature of the modern basal reader, its economics, and use. First, the report provides a history showing how the confluence of business principles, positivistic science, and behavioral psychology led to the transformation of reading textbooks into basal readers. Next, the report examines objectives and subjective factors…

  2. OCD candidate gene SLC1A1/EAAT3 impacts basal ganglia-mediated activity and stereotypic behavior.

    Science.gov (United States)

    Zike, Isaac D; Chohan, Muhammad O; Kopelman, Jared M; Krasnow, Emily N; Flicker, Daniel; Nautiyal, Katherine M; Bubser, Michael; Kellendonk, Christoph; Jones, Carrie K; Stanwood, Gregg; Tanaka, Kenji Fransis; Moore, Holly; Ahmari, Susanne E; Veenstra-VanderWeele, Jeremy

    2017-05-30

    Obsessive-compulsive disorder (OCD) is a chronic, disabling condition with inadequate treatment options that leave most patients with substantial residual symptoms. Structural, neurochemical, and behavioral findings point to a significant role for basal ganglia circuits and for the glutamate system in OCD. Genetic linkage and association studies in OCD point to SLC1A1 , which encodes the neuronal glutamate/aspartate/cysteine transporter excitatory amino acid transporter 3 (EAAT3)/excitatory amino acid transporter 1 (EAAC1). However, no previous studies have investigated EAAT3 in basal ganglia circuits or in relation to OCD-related behavior. Here, we report a model of Slc1a1 loss based on an excisable STOP cassette that yields successful ablation of EAAT3 expression and function. Using amphetamine as a probe, we found that EAAT3 loss prevents expected increases in ( i ) locomotor activity, ( ii ) stereotypy, and ( iii ) immediate early gene induction in the dorsal striatum following amphetamine administration. Further, Slc1a1 -STOP mice showed diminished grooming in an SKF-38393 challenge experiment, a pharmacologic model of OCD-like grooming behavior. This reduced grooming is accompanied by reduced dopamine D 1 receptor binding in the dorsal striatum of Slc1a1 -STOP mice. Slc1a1 -STOP mice also exhibit reduced extracellular dopamine concentrations in the dorsal striatum both at baseline and following amphetamine challenge. Viral-mediated restoration of Slc1a1 /EAAT3 expression in the midbrain but not in the striatum results in partial rescue of amphetamine-induced locomotion and stereotypy in Slc1a1 -STOP mice, consistent with an impact of EAAT3 loss on presynaptic dopaminergic function. Collectively, these findings indicate that the most consistently associated OCD candidate gene impacts basal ganglia-dependent repetitive behaviors.

  3. Nature of extracellular signal that triggers RhoA/ROCK activation for the basal internal anal sphincter tone in humans

    Science.gov (United States)

    Singh, Jagmohan; Kumar, Sumit; Phillips, Benjamin

    2015-01-01

    The extracellular signal that triggers activation of rho-associated kinase (RhoA/ROCK), the major molecular determinant of basal internal anal sphincter (IAS) smooth muscle tone, is not known. Using human IAS tissues, we identified the presence of the biosynthetic machineries for angiotensin II (ANG II), thromboxane A2 (TXA2), and prostaglandin F2α (PGF2α). These end products of the renin-angiotensin system (RAS) (ANG II) and arachidonic acid (TXA2 and PGF2α) pathways and their effects in human IAS vs. rectal smooth muscle (RSM) were studied. A multipronged approach utilizing immunocytochemistry, Western blot analyses, and force measurements was implemented. Additionally, in a systematic analysis of the effects of respective inhibitors along different steps of biosynthesis and those of antagonists, their end products were evaluated either individually or in combination. To further describe the molecular mechanism for the IAS tone via these pathways, we monitored RhoA/ROCK activation and its signal transduction cascade. Data showed characteristically higher expression of biosynthetic machineries of RAS and AA pathways in the IAS compared with the RSM. Additionally, specific inhibition of the arachidonic acid (AA) pathway caused ∼80% decrease in the IAS tone, whereas that of RAS lead to ∼20% decrease. Signal transduction studies revealed that the end products of both AA and RAS pathways cause increase in the IAS tone via activation of RhoA/ROCK. Both AA and RAS (via the release of their end products TXA2, PGF2α, and ANG II, respectively), provide extracellular signals which activate RhoA/ROCK for the maintenance of the basal tone in human IAS. PMID:25882611

  4. Atrophy of the basal ganglia as the initial diagnostic sign of germinoma in the basal ganglia

    Energy Technology Data Exchange (ETDEWEB)

    Okamoto, K.; Ishikawa, K.; Takahashi, N.; Furusawa, T.; Sakai, K. [Department of Radiology, Niigata University Faculty of Medicine (Japan); Ito, J.; Tokiguchi, S. [Department of Radiology, Niigata University Faculty of Dentistry (Japan); Morii, K. [Department of Neurosurgery, Niigata University Brain Research Institute (Japan); Yamada, M. [Department of Pathology, Niigata University Brain Research Institute (Japan)

    2002-05-01

    Germ-cell tumors of the central nervous system generally develop in the midline, but the tumors can also occur in the basal ganglia and/or thalamus. However, MR images have rarely been documented in the early stage of the tumor in these regions. We retrospectively reviewed MR images obtained on admission and approximately 3 years earlier in two patients with germinoma in the basal ganglia, and compared them with CT. In addition to hyperdensity on CT, both hyperintensity on T1-weighted images and a small hyperintense lesion on T2-weighted images were commonly seen in the basal ganglia. These findings may be early MRI signs of germinoma in this region, and the earliest and most characteristic diagnostic feature on MRI was atrophy of the basal ganglia, which was recognizable before development of hemiparesis. (orig.)

  5. The effect of glycogen phosphorolysis on basal glutaminergic transmission.

    Science.gov (United States)

    Mozrzymas, Jerzy; Szczęsny, Tomasz; Rakus, Darek

    2011-01-14

    Astrocytic glycogen metabolism sustains neuronal activity but its impact on basal glutamatergic synaptic transmission is not clear. To address this issue, we have compared the effect of glycogen breakdown inhibition on miniature excitatory postsynaptic currents (mEPSCs) in rat hippocampal pure neuronal culture (PNC) and in astrocyte-neuronal co-cultures (ANCC). Amplitudes of mEPSC in ANCC were nearly twice as large as in PNC with no difference in current kinetics. Inhibition of glycogen phosphorylase reduced mEPSC amplitude by roughly 40% in ANCC being ineffective in PNC. Altogether, these data indicate that astrocyte-neuronal interaction enhances basal mEPSCs in ANCC mainly due to astrocytic glycogen metabolism. Copyright © 2010 Elsevier Inc. All rights reserved.

  6. Choline acetyltransferase expression during periods of behavioral activity and across natural sleep-wake states in the basal forebrain.

    Science.gov (United States)

    Greco, M A; McCarley, R W; Shiromani, P J

    1999-01-01

    The present study examined whether the expression of the messenger RNA encoding the protein responsible for acetylcholine synthesis is associated with sleep-wakefulness. Choline acetyltransferase messenger RNA levels were analysed using a semi-quantitative assay in which reverse transcription was coupled to complementary DNA amplification using the polymerase chain reaction. To examine the relationship between steady-state messenger RNA and behavioral activity, rats were killed during the day (4.00 p.m.) or night (4.00 a.m.), and tissue from the vertical and horizontal limbs of the diagonal bands of Broca was analysed. Choline acetyltransferase messenger RNA levels were higher during the day than during the night. The second study examined more closely the association between choline acetyltransferase messenger RNA levels and individual bouts of wakefulness, slow-wave sleep or rapid eye movement sleep. Choline acetyltransferase messenger RNA levels were low during wakefulness, intermediate in slow-wave sleep and high during rapid eye movement sleep. In contrast, protein activity, measured at a projection site of cholinergic neurons of the basal forebrain, was higher during wakefulness than during sleep. These findings suggest that choline acetyltransferase protein and messenger RNA levels exhibit an inverse relationship during sleep and wakefulness. The increased messenger RNA expression during sleep is consistent with a restorative function of sleep.

  7. Heteroepitaxial growth of basal plane stacking fault free a-plane GaN

    Energy Technology Data Exchange (ETDEWEB)

    Wieneke, Matthias; Hempel, Thomas; Noltemeyer, Martin; Witte, Hartmut; Dadgar, Armin; Blaesing, Juergen; Christen, Juergen; Krost, Alois [Otto-von-Guericke Universitaet Magdeburg, FNW/IEP, Magdeburg (Germany)

    2010-07-01

    Growth of light emitting quantum-wells based on a-plane GaN is a possibility to reduce or even to avoid polarization correlated luminescence red shift and reduction of radiative recombination efficiency. But until now heteroepitaxially grown a-plane GaN films are characterized by a poor crystalline quality expressed by a high density of basal plane stacking faults (BSF) and partial dislocations. We present Si doped a-plane GaN films grown on r-plane sapphire substrates by metal organic vapor phase epitaxy using high temperature AlGaN nucleation layers. FE-SEM images revealed three dimensionally grown GaN crystallites sized up to tenth micrometer in the basal plane and a few tenth micrometers along the c-axes. Though, the full width at half maxima of the X-ray diffraction {omega}-scans of the in-plane GaN(1 anti 100) and GaN(0002) Bragg reflections exhibited a very high crystal quality. Furthermore, luminescence spectra were dominated by near band gap emission, while there was no separated peak of the basal plane stacking fault. In summary we present heteroepitaxially grown a-plane GaN without an evidence of basal plane stacking faults in X-ray diffraction measurements and luminescence spectra.

  8. In vivo assessment of optical properties of basal cell carcinoma and differentiation of BCC subtypes by high-definition optical coherence tomography

    DEFF Research Database (Denmark)

    Boone, Marc; Suppa, Mariano; Miyamoto, Makiko

    2016-01-01

    High-definition optical coherence tomography (HD-OCT) features of basal cell carcinoma (BCC) have recently been defined. We assessed in vivo optical properties (IV-OP) of BCC, by HD-OCT. Moreover their critical values for BCC subtype differentiation were determined. The technique of semi-log plot...

  9. Sclerodermiform basal cell carcinoma: how much can we rely on dermatoscopy to differentiate from non-aggressive basal cell carcinomas? Analysis of 1256 cases.

    Science.gov (United States)

    Husein-ElAhmed, Husein

    2018-03-01

    The behaviour of each basal cell carcinoma is known to be different according to the histological growth pattern. Among these aggressive lesions, sclerodermiform basal cell carcinomas are the most common type. This is a challenging-to-treat lesion due to its deep tissue invasion, rapid growth, risk of metastasis and overall poor prognosis if not diagnosed in early stages. To investigate if sclerodermiform basal cell carcinomas are diagnosed later compared to non-sclerodermiform basal cell carcinoma Method: All lesions excised from 2000 to 2010 were included. A pathologist classified the lesions in two cohorts: one with specimens of non-aggressive basal cell carcinoma (superficial, nodular and pigmented), and other with sclerodermiform basal cell carcinoma. For each lesion, we collected patient's information from digital medical records regarding: gender, age when first attending the clinic and the tumor location. 1256 lesions were included, out of which 296 (23.6%) corresponded to sclerodermiform basal cell carcinoma, whereas 960 (76.4%) were non-aggressive subtypes of basal cell carcinoma. The age of diagnosis was: 72.78±12.31 years for sclerodermiform basal cell and 69.26±13.87 years for non-aggressive basal cell carcinoma (Pbasal cell carcinomas are diagnosed on average 3.52 years later than non-aggressive basal cell carcinomas. Sclerodermiform basal cell carcinomas were diagnosed 3.40 years and 2.34 years later than non-aggressive basal cell carcinomas in younger and older patients respectively (P=.002 and P=.03, respectively). retrospective design. The diagnostic accuracy and primary clinic conjecture of sclerodermiform basal cell carcinomas is quite low compared to other forms of basal cell carcinoma such as nodular, superficial and pigmented. The dermoscopic vascular patterns, which is the basis for the diagnosis of non-melanocytic nonpigmented skin tumors, may not be particularly useful in identifying sclerodermiform basal cell carcinomas in early stages

  10. Ultra-high field magnetic resonance imaging of the basal ganglia and related structures

    NARCIS (Netherlands)

    Plantinga, B.R.; Temel, Y.; Roebroeck, A.; Uludag, K.; Ivanov, D.; Kuijf, M.L.; ter Haar Romeny, B.M.

    2014-01-01

    Deep brain stimulation is a treatment for Parkinson's disease and other related disorders, involving the surgical placement of electrodes in the deeply situated basal ganglia or thalamic structures. Good clinical outcome requires accurate targeting. However, due to limited visibility of the target

  11. Hemodynamics in the cerebral cortex and basal ganglia

    International Nuclear Information System (INIS)

    Yamaguchi, Shinya; Fukuyama, Hidenao; Yamauchi, Hiroshi; Kimura, Jun

    1991-01-01

    We examined ten healthy volunteers using positron emission tomography (PET) in order to elucidate regional changes and correlations in the cerebral circulation and oxygen metabolism. We also studied eight lacunar stroke patients so as to disclose the influences of vascular risk factors and aging on the cerebral blood flow and metabolism. We can conclude from our result as follows: (1) Cerebral blood volume (CBV) was minimum in the basal ganglia and cerebral blood flow (CBF)/CBV ratio was higher than that of cerebral cortex in healthy volunteers; (2) CBF of gray matter in healthy volunteers correlated with CBV and cerebral metabolic rate of oxygen where oxygen extraction fraction inversely correlated with CBF, CBV, and CBF/CBV; and (3) the basal ganglia CBF/CBV ratio in lacunar stroke patients was lower than that of healthy volunteers. These findings suggested that the perfusion pressure in the basal ganglia was so high in the normal condition than the angionecrosis or occlusion in the perforating arteries would be induced, especially in the aged and hypertensive patients. (author)

  12. Migraine attacks the Basal Ganglia

    Directory of Open Access Journals (Sweden)

    Bigal Marcelo

    2011-09-01

    Full Text Available Abstract Background With time, episodes of migraine headache afflict patients with increased frequency, longer duration and more intense pain. While episodic migraine may be defined as 1-14 attacks per month, there are no clear-cut phases defined, and those patients with low frequency may progress to high frequency episodic migraine and the latter may progress into chronic daily headache (> 15 attacks per month. The pathophysiology of this progression is completely unknown. Attempting to unravel this phenomenon, we used high field (human brain imaging to compare functional responses, functional connectivity and brain morphology in patients whose migraine episodes did not progress (LF to a matched (gender, age, age of onset and type of medication group of patients whose migraine episodes progressed (HF. Results In comparison to LF patients, responses to pain in HF patients were significantly lower in the caudate, putamen and pallidum. Paradoxically, associated with these lower responses in HF patients, gray matter volume of the right and left caudate nuclei were significantly larger than in the LF patients. Functional connectivity analysis revealed additional differences between the two groups in regard to response to pain. Conclusions Supported by current understanding of basal ganglia role in pain processing, the findings suggest a significant role of the basal ganglia in the pathophysiology of the episodic migraine.

  13. Genetic activation, inactivation and deletion reveal a limited and nuanced role for somatostatin-containing basal forebrain neurons in behavioral state control.

    Science.gov (United States)

    Anaclet, Christelle; De Luca, Roberto; Venner, Anne; Malyshevskaya, Olga; Lazarus, Michael; Arrigoni, Elda; Fuller, Patrick M

    2018-05-07

    Recent studies have identified an especially important role for basal forebrain GABAergic (BF VGAT ) neurons in the regulation of behavioral waking and fast cortical rhythms associated with cognition. However, BF VGAT neurons comprise several neurochemically and anatomically distinct sub-populations, including parvalbumin- and somatostatin-containing BF VGAT neurons (BF Parv and BF SOM ), and it was recently reported that optogenetic activation of BF SOM neurons increases the probability of a wakefulness to non-rapid-eye movement (NREM) sleep transition when stimulated during the animal's rest period. This finding was unexpected given that most BF SOM neurons are not NREM sleep active and that central administration of the synthetic SOM analog, octreotide, suppresses NREM sleep or increases REM sleep. Here we employed a combination of genetically-driven chemogenetic and optogenetic activation, chemogenetic inhibition and ablation approaches to further explore the in vivo role of BF SOM neurons in arousal control. Our findings indicate that acute activation or inhibition of BF SOM neurons is neither wakefulness- nor NREM sleep-promoting, is without significant effect on the EEG, and that chronic loss of these neurons is without effect on total 24h sleep amounts, although a small but significant increase in waking was observed in the lesioned mice during the early active period. Our in vitro cell recordings further reveal electrophysiological heterogeneity in BF SOM neurons, specifically suggesting at least two distinct sub-populations. Taken together our data support the more nuanced view that BF SOM are electrically heterogeneous and are not NREM sleep- or wake-promoting per se , but may exert, in particular during the early active period, a modest inhibitory influence on arousal circuitry. SIGNIFICANCE STATEMENT The cellular basal forebrain (BF) is a highly complex area of the brain that is implicated in a wide-range of higher-level neurobiological processes

  14. Dynamic stereotypic responses of Basal Ganglia neurons to subthalamic nucleus high-frequency stimulation in the parkinsonian primate.

    Science.gov (United States)

    Moran, Anan; Stein, Edward; Tischler, Hadass; Belelovsky, Katya; Bar-Gad, Izhar

    2011-01-01

    Deep brain stimulation (DBS) in the subthalamic nucleus (STN) is a well-established therapy for patients with severe Parkinson's disease (PD); however, its mechanism of action is still unclear. In this study we explored static and dynamic activation patterns in the basal ganglia (BG) during high-frequency macro-stimulation of the STN. Extracellular multi-electrode recordings were performed in primates rendered parkinsonian using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Recordings were preformed simultaneously in the STN and the globus pallidus externus and internus. Single units were recorded preceding and during the stimulation. During the stimulation, STN mean firing rate dropped significantly, while pallidal mean firing rates did not change significantly. The vast majority of neurons across all three nuclei displayed stimulation driven modulations, which were stereotypic within each nucleus but differed across nuclei. The predominant response pattern of STN neurons was somatic inhibition. However, most pallidal neurons demonstrated synaptic activation patterns. A minority of neurons across all nuclei displayed axonal activation. Temporal dynamics were observed in the response to stimulation over the first 10 seconds in the STN and over the first 30 seconds in the pallidum. In both pallidal segments, the synaptic activation response patterns underwent delay and decay of the magnitude of the peak response due to short term synaptic depression. We suggest that during STN macro-stimulation the STN goes through a functional ablation as its upper bound on information transmission drops significantly. This notion is further supported by the evident dissociation between the stimulation driven pre-synaptic STN somatic inhibition and the post-synaptic axonal activation of its downstream targets. Thus, BG output maintains its firing rate while losing the deleterious effect of the STN. This may be a part of the mechanism leading to the beneficial effect of DBS in PD.

  15. Using a hybrid neuron in physiologically inspired models of the basal ganglia

    Directory of Open Access Journals (Sweden)

    Corey Michael Thibeault

    2013-07-01

    Full Text Available Our current understanding of the basal ganglia has facilitated the creation of computational models that have contributed novel theories, explored new functional anatomy and demonstrated results complementing physiological experiments. However, the utility of these models extends beyond these applications. Particularly in neuromorphic engineering, where the basal ganglia's role in computation is important for applications such as power efficient autonomous agents and model-based control strategies. The neurons used in existing computational models of the basal ganglia however, are not amenable for many low-power hardware implementations. Motivated by a need for more hardware accessible networks, we replicate four published models of the basal ganglia, spanning single neuron and small networks, replacing the more computationally expensive neuron models with an Izhikevich hybrid neuron. This begins with a network modeling action-selection, where the basal activity levels and the ability to appropriately select the most salient input is reproduced. A Parkinson's disease model is then explored under normal conditions, Parkinsonian conditions and during subthalamic nucleus deep brain stimulation. The resulting network is capable of replicating the loss of thalamic relay capabilities in the Parkinsonian state and its return under deep brain stimulation. This is also demonstrated using a network capable of action-selection. Finally, a study of correlation transfer under different patterns of Parkinsonian activity is presented. These networks successfully captured the significant results of the originals studies. This not only creates a foundation for neuromorphic hardware implementations but may also support the development of large-scale biophysical models. The former potentially providing a way of improving the efficacy of deep brain stimulation and the latter allowing for the efficient simulation of larger more comprehensive networks.

  16. Basal μ-opioid receptor availability in the amygdala predicts the inhibition of pain-related brain activity during heterotopic noxious counter-stimulation.

    Science.gov (United States)

    Piché, Mathieu; Watanabe, Nobuhiro; Sakata, Muneyuki; Oda, Keiichi; Toyohara, Jun; Ishii, Kenji; Ishiwata, Kiichi; Hotta, Harumi

    2014-01-01

    The aim of this study was to investigate the association between the magnitude of anti-nociceptive effects induced by heterotopic noxious counter-stimulation (HNCS) and the basal μ-opioid receptor availability in the amygdala. In 8 healthy volunteers (4 females and 4 males), transcutaneous electrical stimulation was applied to the right sural nerve to produce the nociceptive flexion reflex (RIII-reflex), moderate pain, and scalp somatosensory evoked potentials (SEPs). Immersion of the left hand in cold water for 20min was used as HNCS. In a separate session, basal μ-opioid receptor availability was measured using positron emission tomography with the radiotracer [(11)C]carfentanil. HNCS produced a reduction of the P260 amplitude (pbasal μ-opioid receptor availability in the amygdala on the right (R(2)=0.55, p=0.03) with a similar trend on the left (R(2)=0.24, p=0.22). Besides, HNCS did not induce significant changes in pain and RIII-reflex amplitude (p>0.05). These results suggest that activation of μ-opioid receptors in the amygdala may contribute to the anti-nociceptive effects of HNCS. The lack of RIII-reflex modulation further suggests that μ-opioid receptor activation in the amygdala contributes to decrease pain-related brain activity through a cerebral mechanism independent of descending modulation. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  17. Interindividual differences in stress sensitivity: basal and stress-induced cortisol levels differentially predict neural vigilance processing under stress.

    Science.gov (United States)

    Henckens, Marloes J A G; Klumpers, Floris; Everaerd, Daphne; Kooijman, Sabine C; van Wingen, Guido A; Fernández, Guillén

    2016-04-01

    Stress exposure is known to precipitate psychological disorders. However, large differences exist in how individuals respond to stressful situations. A major marker for stress sensitivity is hypothalamus-pituitary-adrenal (HPA)-axis function. Here, we studied how interindividual variance in both basal cortisol levels and stress-induced cortisol responses predicts differences in neural vigilance processing during stress exposure. Implementing a randomized, counterbalanced, crossover design, 120 healthy male participants were exposed to a stress-induction and control procedure, followed by an emotional perception task (viewing fearful and happy faces) during fMRI scanning. Stress sensitivity was assessed using physiological (salivary cortisol levels) and psychological measures (trait questionnaires). High stress-induced cortisol responses were associated with increased stress sensitivity as assessed by psychological questionnaires, a stronger stress-induced increase in medial temporal activity and greater differential amygdala responses to fearful as opposed to happy faces under control conditions. In contrast, high basal cortisol levels were related to relative stress resilience as reflected by higher extraversion scores, a lower stress-induced increase in amygdala activity and enhanced differential processing of fearful compared with happy faces under stress. These findings seem to reflect a critical role for HPA-axis signaling in stress coping; higher basal levels indicate stress resilience, whereas higher cortisol responsivity to stress might facilitate recovery in those individuals prone to react sensitively to stress. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  18. Habituation to low or high protein intake does not modulate basal or postprandial muscle protein synthesis rates: a randomized trial.

    Science.gov (United States)

    Gorissen, Stefan Hm; Horstman, Astrid Mh; Franssen, Rinske; Kouw, Imre Wk; Wall, Benjamin T; Burd, Nicholas A; de Groot, Lisette Cpgm; van Loon, Luc Jc

    2017-02-01

    Muscle mass maintenance is largely regulated by basal muscle protein synthesis rates and the ability to increase muscle protein synthesis after protein ingestion. To our knowledge, no previous studies have evaluated the impact of habituation to either low protein intake (LOW PRO) or high protein intake (HIGH PRO) on the postprandial muscle protein synthetic response. We assessed the impact of LOW PRO compared with HIGH PRO on basal and postprandial muscle protein synthesis rates after the ingestion of 25 g whey protein. Twenty-four healthy, older men [age: 62 ± 1 y; body mass index (in kg/m 2 ): 25.9 ± 0.4 (mean ± SEM)] participated in a parallel-group randomized trial in which they adapted to either a LOW PRO diet (0.7 g · kg -1 · d -1 ; n = 12) or a HIGH PRO diet (1.5 g · kg -1 · d -1 ; n = 12) for 14 d. On day 15, participants received primed continuous l-[ring- 2 H 5 ]-phenylalanine and l-[1- 13 C]-leucine infusions and ingested 25 g intrinsically l-[1- 13 C]-phenylalanine- and l-[1- 13 C]-leucine-labeled whey protein. Muscle biopsies and blood samples were collected to assess muscle protein synthesis rates as well as dietary protein digestion and absorption kinetics. Plasma leucine concentrations and exogenous phenylalanine appearance rates increased after protein ingestion (P 0.05). Plasma exogenous phenylalanine availability over the 5-h postprandial period was greater after LOW PRO than after HIGH PRO (61% ± 1% compared with 56% ± 2%, respectively; P protein synthesis rates increased from 0.031% ± 0.004% compared with 0.039% ± 0.007%/h in the fasted state to 0.062% ± 0.005% compared with 0.057% ± 0.005%/h in the postprandial state after LOW PRO compared with HIGH PRO, respectively (P protein-derived amino acids in the circulation and does not lower basal muscle protein synthesis rates or increase postprandial muscle protein synthesis rates after ingestion of 25 g protein in older men. This trial was registered at clinicaltrials.gov as NCT

  19. Basal encephalocele and morning glory syndrome.

    Science.gov (United States)

    Caprioli, J; Lesser, R L

    1983-01-01

    Basal encephaloceles are often associated with other midline anomalies such as hypertelorism, broad nasal root, cleft lip, and cleft palate. Optic disc anomalies such as pallor, dysplasia, optic pit, coLoboma, and megalopapilla have been reported to occur in patients with basal encephalocele We report a case of a child with a sphenoethmoidal encephalocele and morning glory syndrome of the optic nerve. The presence of such optic nerve anomalies with facial midline anomalies should alert the clinician to the possible presence of a basal encephalocele. Images PMID:6849854

  20. Do gap junctions regulate synchrony in the parkinsonian basal ganglia?

    NARCIS (Netherlands)

    Schwab, B.C.

    2016-01-01

    Patients with Parkinson’s disease (PD) typically suffer severely from different types of symptoms. Motor symptoms, restricting the patients’ ability to perform controlled movements in daily life, are of special clinical interest and have been related to neural activity in the basal ganglia.

  1. Effect of aqueous extract of mango kernel (Mangifera Indica on basal activity of virgin rat uterine smooth muscle: role of muscarinic receptors

    Directory of Open Access Journals (Sweden)

    Mehdi Noureddini

    2017-04-01

    Full Text Available Background: Mango belongs to the Anacardiaceae and the extracts from its stems, leaves, fruit and kernel are reported to affect smooth muscle contractility. We studied the role of cholinergic muscarinic receptors for the effects of aqueous extract of mango kernel (Mangifera indica on the basal activity of virgin rat uterine smooth muscle. Materials and Methods: In this experimental study, mid-sections (n=24 of the uterine of healthy virgin rats were placed in an organ bath containing carbonated Tyrode’s solution under 1 g tension. The cumulative effects of the aqueous extracts of mango kernel (0.002, 0.02, 0.2, 2, 20, 200, and 2000 μg/mL or extract vehicle (Tyrode’s solution in the presence or absence of atropine were examined by isometric method using the strength, frequency and contractile activity of uterine smooth muscle. Results: The cumulative concentrations (0.002-20 µg/ml of mango kernel aqueous extract was significantly decreased the strength, frequency and contractile activity of uterine smooth muscle, but the contractile activity was returned to the basal level at the concentrations of 200 and 2000 µg/ml. Atropine (1 µM could not significantly change the effects of cumulative use of extract on the strength and contractile activity of uterine smooth muscle, but it significantly enhanced the contractile frequency at low concentrations. Conclusion: The effects of aqueous extract of mango kernel on the activity of the uterine smooth muscle might not be through cholinergic muscarinic receptors and atropine could enhance the effects of the extract on frequency through other receptors.

  2. 980nm laser for difficult-to-treat basal cell carcinoma

    Science.gov (United States)

    Derjabo, A. D.; Cema, I.; Lihacova, I.; Derjabo, L.

    2013-06-01

    Begin basal cell carcinoma (BCC) is most common skin cancer over the world. There are around 20 modalities for BCC treatment. Laser surgery is uncommon option. We demonstrate our long term follow up results. Aim: To evaluate long term efficacy of a 980nm diode laser for the difficult-to-treat basal cell carcinoma. Materials and Methods: 167 patients with 173 basal cell carcinoma on the nose were treated with a 980 nm diode laser from May 1999 till May 2005 at Latvian Oncology center. All tumors were morphologically confirmed. 156 patients were followed for more than 5 years. Results: The lowest recurrence rate was observed in cases of superficial BCC, diameterConclusions: 980 nm diode laser is useful tool in dermatology with high long term efficacy, good acceptance by the patients and good cosmetics results.

  3. Basal levels of metabolic activity are elevated in Genetic Absence Epilepsy Rats from Strasbourg (GAERS): measurement of regional activity of cytochrome oxidase and lactate dehydrogenase by histochemistry.

    Science.gov (United States)

    Dufour, Franck; Koning, Estelle; Nehlig, Astrid

    2003-08-01

    The Genetic Absence Epilepsy Rats from Strasbourg (GAERS) are considered an isomorphic, predictive, and homologous model of human generalized absence epilepsy. It is characterized by the expression of spike-and-wave discharges in the thalamus and cortex. In this strain, basal regional rates of cerebral glucose utilization measured by the quantitative autoradiographic [(14)C]2-deoxyglucose technique display a widespread consistent increase compared to a selected strain of genetically nonepileptic rats (NE). In order to verify whether these high rates of glucose metabolism are paralleled by elevated activities of the enzymes of the glycolytic and tricarboxylic acid cycle pathways, we measured by histochemistry the regional activity of the two key enzymes of glucose metabolism, lactate dehydrogenase (LDH) for the anaerobic pathway and cytochrome oxidase (CO) for the aerobic pathway coupled to oxidative phosphorylation. CO and LDH activities were significantly higher in GAERS than in NE rats in 24 and 28 of the 30 brain regions studied, respectively. The differences in CO and LDH activity between both strains were widespread, affected all brain systems studied, and ranged from 12 to 63%. The data of the present study confirm the generalized increase in cerebral glucose metabolism in GAERS, occurring both at the glycolytic and at the oxidative step. However, they still do not allow us to understand why the ubiquitous mutation(s) generates spike-and-wave discharges only in the thalamocortical circuit.

  4. Inter regional correlations of glucose metabolism between the basal ganglia and different cortical areas: an ultra-high resolution PET/MRI fusion study using 18F-FDG

    International Nuclear Information System (INIS)

    Kim, J.H.; Son, Y.D.; Kim, H.K.; Oh, C.H.; Kim, J.M.; Kim, Y.B.; Lee, C.

    2018-01-01

    Basal ganglia have complex functional connections with the cerebral cortex and are involved in motor control, executive functions of the forebrain, such as the planning of movement, and cognitive behaviors based on their connections. The aim of this study was to provide detailed functional correlation patterns between the basal ganglia and cerebral cortex by conducting an inter regional correlation analysis of the 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET) data based on precise structural information. Fifteen participants were scanned with 7-Tesla magnetic resonance imaging (MRI) and high resolution research tomography (HRRT)-PET fusion system using 18 F-FDG. For detailed inter regional correlation analysis, 24 subregions of the basal ganglia including pre-commissural dorsal caudate, post-commissural caudate, pre-commissural dorsal putamen, post-commissural putamen, internal globus pallidus, and external globus pallidus and 80 cerebral regions were selected as regions of interest on the MRI image and their glucose metabolism were calculated from the PET images. Pearson's product-moment correlation analysis was conducted for the inter regional correlation analysis of the basal ganglia. Functional correlation patterns between the basal ganglia and cerebral cortex were not only consistent with the findings of previous studies, but also showed new functional correlation between the dorsal striatum (i.e., caudate nucleus and putamen) and insula. In this study, we established the detailed basal ganglia subregional functional correlation patterns using 18 F-FDG PET/MRI fusion imaging. Our methods and results could potentially be an important resource for investigating basal ganglia dysfunction as well as for conducting functional studies in the context of movement and psychiatric disorders. (author)

  5. Correlation transfer from basal ganglia to thalamus in Parkinson's disease

    Science.gov (United States)

    Pamela, Reitsma; Brent, Doiron; Jonathan, Rubin

    2011-01-01

    Spike trains from neurons in the basal ganglia of parkinsonian primates show increased pairwise correlations, oscillatory activity, and burst rate compared to those from neurons recorded during normal brain activity. However, it is not known how these changes affect the behavior of downstream thalamic neurons. To understand how patterns of basal ganglia population activity may affect thalamic spike statistics, we study pairs of model thalamocortical (TC) relay neurons receiving correlated inhibitory input from the internal segment of the globus pallidus (GPi), a primary output nucleus of the basal ganglia. We observe that the strength of correlations of TC neuron spike trains increases with the GPi correlation level, and bursty firing patterns such as those seen in the parkinsonian GPi allow for stronger transfer of correlations than do firing patterns found under normal conditions. We also show that the T-current in the TC neurons does not significantly affect correlation transfer, despite its pronounced effects on spiking. Oscillatory firing patterns in GPi are shown to affect the timescale at which correlations are best transferred through the system. To explain this last result, we analytically compute the spike count correlation coefficient for oscillatory cases in a reduced point process model. Our analysis indicates that the dependence of the timescale of correlation transfer is robust to different levels of input spike and rate correlations and arises due to differences in instantaneous spike correlations, even when the long timescale rhythmic modulations of neurons are identical. Overall, these results show that parkinsonian firing patterns in GPi do affect the transfer of correlations to the thalamus. PMID:22355287

  6. Basal erosion: barrier to earthquake propagation? Insight from the northern chilean forearc

    Science.gov (United States)

    Cubas, N.

    2017-12-01

    Subducted topographic features have often been suspected as barriers to large earthquake propagation. These features would induce basal erosion, leading to a large network of fractures impeding large nucleation or shear localization. Looking for correlation between basal erosion and megathrust ruptures is thus critical nowadays to understand earthquake mechanics and infer rupture scenarios. In this study, we propose to seek possible location of basal erosion from the forearc morphology by applying the critical taper theory. We focus on the North Chile subduction zone that has experienced four major earthquakes during the last two decades and where basal erosion and seamount subduction have already been suspected. Basal erosion should occur when the basal friction approaches the internal friction. We thus seek what part of the forearc is at critical state and select areas for which the two frictions are almost equal. We find a large band, located at 25km depth, from the Mejillones peninsula to the Iquique region at critical state with very high basal friction. The critical areas seem to surround the Tocopilla 2007 Mw 7.7 and the Iquique 2014 Mw 8.1 ruptures. When compared with the interseismic coupling, except for the Tocopilla segment, the critical areas are located in low-coupled zones. More interestingly, the reported normal faults of the forearc do not appear above the erosional areas but rather between them. These normal faults are systematically located above locked patches and seismic asperities. These areas are actually at extensional critical state and characterized by a very low effective friction. We thus suspect the extensional features to be related to earthquakes rather than basal erosion. We then look for similar relationships along the Sumatra subduction zone to see if basal erosion is a common process. The Tocopilla and Iquique earthquakes ruptured only part of the northern Chile seismic gap although the full segment was ready for a new large

  7. Neglected Giant Scalp Basal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Anne Kristine Larsen, MD

    2014-03-01

    Full Text Available Summary: Rarely, basal cell carcinoma grows to a giant size, invading the underlying deep tissue and complicating the treatment and reconstruction modalities. A giant basal cell carcinoma on the scalp is in some cases treated with a combination of surgery and radiation therapy, resulting in local control, a satisfactory long-term cosmetic and functional result. We present a case with a neglected basal cell scalp carcinoma, treated with wide excision and postoperative radiotherapy, reconstructed with a free latissimus dorsi flap. The cosmetic result is acceptable and there is no sign of recurrence 1 year postoperatively.

  8. Interaction of synchronized dynamics in cortex and basal ganglia in Parkinson's disease.

    Science.gov (United States)

    Ahn, Sungwoo; Zauber, S Elizabeth; Worth, Robert M; Witt, Thomas; Rubchinsky, Leonid L

    2015-09-01

    Parkinson's disease pathophysiology is marked by increased oscillatory and synchronous activity in the beta frequency band in cortical and basal ganglia circuits. This study explores the functional connections between synchronized dynamics of cortical areas and synchronized dynamics of subcortical areas in Parkinson's disease. We simultaneously recorded neuronal units (spikes) and local field potentials (LFP) from subthalamic nucleus (STN) and electroencephalograms (EEGs) from the scalp in parkinsonian patients, and analysed the correlation between the time courses of the spike-LFP synchronization and inter-electrode EEG synchronization. We found the (non-invasively obtained) time course of the synchrony strength between EEG electrodes and the (invasively obtained) time course of the synchrony between spiking units and LFP in STN to be weakly, but significantly, correlated with each other. This correlation is largest for the bilateral motor EEG synchronization, followed by bilateral frontal EEG synchronization. Our observations suggest that there may be multiple functional modes by which the cortical and basal ganglia circuits interact with each other in Parkinson's disease: not only may synchronization be observed between some areas in cortex and the basal ganglia, but also synchronization within cortex and within basal ganglia may be related, suggesting potentially a more global functional interaction. More coherent dynamics in one brain region may modulate or activate the dynamics of another brain region in a more powerful way, causing correlations between changes in synchrony strength in the two regions. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  9. High basal metabolic rates in shorebirds while in the Arctic: a circumpolar view

    NARCIS (Netherlands)

    Lindström, A.; Klaassen, M.R.J.

    2003-01-01

    The basal metabolic rate (BMR) of Old World long-distance-migrant shorebirds has been found to vary along their migration route. On average, BMR is highest in the Arctic at the start of fall migration, intermediate at temperate latitudes, and lowest on the tropical wintering grounds. As a test of

  10. miRNA-135b Contributes to Triple Negative Breast Cancer Molecular Heterogeneity: Different Expression Profile in Basal-like Versus non-Basal-like Phenotypes.

    Science.gov (United States)

    Uva, Paolo; Cossu-Rocca, Paolo; Loi, Federica; Pira, Giovanna; Murgia, Luciano; Orrù, Sandra; Floris, Matteo; Muroni, Maria Rosaria; Sanges, Francesca; Carru, Ciriaco; Angius, Andrea; De Miglio, Maria Rosaria

    2018-01-01

    The clinical and genetic heterogeneity of Triple Negative Breast Cancer (TNBC) and the lack of unambiguous molecular targets contribute to the inadequacy of current therapeutic options for these variants. MicroRNAs (miRNA) are a class of small highly conserved regulatory endogenous non-coding RNA, which can alter the expression of genes encoding proteins and may play a role in the dysregulation of cellular pathways. Our goal was to improve the knowledge of the molecular pathogenesis of TNBC subgroups analyzing the miRNA expression profile, and to identify new prognostic and predictive biomarkers. We conducted a human miRNome analysis by TaqMan Low Density Array comparing different TNBC subtypes, defined by immunohistochemical basal markers EGFR and CK5/6. RT-qPCR confirmed differential expression of microRNAs. To inspect the function of the selected targets we perform Gene Ontology and KEGG enrichment analysis. We identified a single miRNA signature given by miR-135b expression level, which was strictly related to TNBC with basal-like phenotype. miR-135b target analysis revealed a role in the TGF-beta, WNT and ERBB pathways. A significant positive correlation was identified between neoplastic proliferative index and miR-135b expression. These findings confirm the oncogenic roles of miR-135b in the pathogenesis of TNBC expressing basal markers. A potential negative prognostic role of miR-135b overexpression might be related to the positive correlation with high proliferative index. Our study implies potential clinical applications: miR-135b could be a potential therapeutic target in basal-like TNBCs.

  11. The future of basal insulin supplementation

    NARCIS (Netherlands)

    Simon, Airin C. R.; DeVries, J. Hans

    2011-01-01

    This review presents an overview of the candidates for an improved basal insulin in the pharmaceutical pipeline. The first new basal insulin to enter the market is most likely insulin degludec (IDeg), currently reporting in phase 3 of development, from Novo Nordisk (Bagsvaerd, Denmark). IDeg has a

  12. Adaptive autoregressive identification with spectral power decomposition for studying movement-related activity in scalp EEG signals and basal ganglia local field potentials

    Science.gov (United States)

    Foffani, Guglielmo; Bianchi, Anna M.; Priori, Alberto; Baselli, Giuseppe

    2004-09-01

    We propose a method that combines adaptive autoregressive (AAR) identification and spectral power decomposition for the study of movement-related spectral changes in scalp EEG signals and basal ganglia local field potentials (LFPs). This approach introduces the concept of movement-related poles, allowing one to study not only the classical event-related desynchronizations (ERD) and synchronizations (ERS), which correspond to modulations of power, but also event-related modulations of frequency. We applied the method to analyze movement-related EEG signals and LFPs contemporarily recorded from the sensorimotor cortex, the globus pallidus internus (GPi) and the subthalamic nucleus (STN) in a patient with Parkinson's disease who underwent stereotactic neurosurgery for the implant of deep brain stimulation (DBS) electrodes. In the AAR identification we compared the whale and the exponential forgetting factors, showing that the whale forgetting provides a better disturbance rejection and it is therefore more suitable to investigate movement-related brain activity. Movement-related power modulations were consistent with previous studies. In addition, movement-related frequency modulations were observed from both scalp EEG signals and basal ganglia LFPs. The method therefore represents an effective approach to the study of movement-related brain activity.

  13. Activation of the Basal Forebrain by the Orexin/Hypocretin Neurons: Orexin International Symposium

    Science.gov (United States)

    Arrigoni, Elda; Mochizuki, Takatoshi; Scammell, Thomas E.

    2010-01-01

    The orexin neurons play an essential role in driving arousal and in maintaining normal wakefulness. Lack of orexin neurotransmission produces a chronic state of hypoarousal characterized by excessive sleepiness, frequent transitions between wake and sleep, and episodes of cataplexy. A growing body of research now suggests that the basal forebrain (BF) may be a key site through which the orexin-producing neurons promote arousal. Here we review anatomical, pharmacological and electrophysiological studies on how the orexin neurons may promote arousal by exciting cortically-projecting neurons of the BF. Orexin fibers synapse on BF cholinergic neurons and orexin-A is released in the BF during waking. Local application of orexins excites BF cholinergic neurons, induces cortical release of acetylcholine, and promotes wakefulness. The orexin neurons also contain and probably co-release the inhibitory neuropeptide dynorphin. We found that orexin-A and dynorphin have specific effects on different classes of BF neurons that project to the cortex. Cholinergic neurons were directly excited by orexin-A, but did not respond to dynorphin. Non-cholinergic BF neurons that project to the cortex seem to comprise at least two populations with some directly excited by orexin that may represent wake-active, GABAergic neurons, whereas others did not respond to orexin but were inhibited by dynorphin and may be sleep-active, GABAergic neurons. This evidence suggests that the BF is a key site through which orexins activate the cortex and promotes behavioral arousal. In addition, orexins and dynorphin may act synergistically in the BF to promote arousal and improve cognitive performance. PMID:19723027

  14. Basal Metabolic Rate and Energy Expenditure of Rural Farmers in ...

    African Journals Online (AJOL)

    Measurement of basal metabolic rate (BMR) provides an important baseline for the determination of an individual's total energy requirement. The study sought to establish human energy expenditure of rural farmers in Magubike village in Tanzania, through determination of BMR, physical activity level (PAL) and total energy ...

  15. Modern basal insulin analogs: An incomplete story

    OpenAIRE

    Singh, Awadhesh Kumar; Gangopadhyay, Kalyan Kumar

    2014-01-01

    The currently available basal insulin does not completely mimic the endogenous insulin secretion. This has continued to promote the search for ideal basal insulin. The newer basal insulin have primarily focused on increasing the duration of action, reducing variability, and reducing the incidence of hypoglycemia, particularly nocturnal. However, the changing criteria of hypoglycemia within a short span of a few years along with the surprising introduction of major cardiac events as another ou...

  16. Computerized tomographic diagnosis of basal skull fracture

    International Nuclear Information System (INIS)

    Tanaka, Tokutaro; Shimoyama, Ichiro; Endoh, Mitsutoshi; Ninchoji, Toshiaki; Uemura, Kenichi.

    1984-01-01

    The diagnosis of basal skull fractures used to be difficult, particularly on the basis of routine skull roentgenography alone. We have now examined the diagnostic value of conventional computerized tomography in basal skull fractures. We studied 82 cases clinically diagnosed as basal skull fractures. We examined them based on at least one of the following computerized tomographic criteria for basal skull fractures: 1) fracture line(s), 2) intracranial air, 3) fluid in the paranasal sinuses, and 4) fluid in the middle ear, including the mastoid air cells. The signs of the fracture line and of the intracranial air are definite indications of basal skull fracture, but the signs of fluid in the paranasal sinuses and/or in the middle ear are not definite. When combined, however, with such other clinical signs as black eye, Battle's sign, CSF leakage, CSF findings, and profuse nasal or ear bleeding, the diagnosis is more reliable. Seventy cases (85.4%) in this series had basal skull fractures according to our computerized tomographic criteria. Among them , 26 cases (31.7%) were diagnosed with fracture lines, 17 cases (20.7%) with intracranial air, 16 cases (19.5%) with fluid in the paranasal sinuses, 10 cases (12.2%) with fluid in the middle ear, and one case (1.2%) with fluid in both. Twelve cases (14.6%) of the 82 cases clinically diagnosed as basal skull fractures could not have been diagnosed on our computerized tomographic criteria alone. We diagnosed them because of CSF leakage, CSF findings, surgical findings, etc. (author)

  17. Sustained high basal motion of the Greenland ice sheet revealed by borehole deformation

    DEFF Research Database (Denmark)

    Ryser, Claudia; Luethi, Martin P.; Andrews, Lauren C.

    2014-01-01

    amount of basal motion contribution to surface velocity of 44-73% in winter, and up to 90% in summer. Measured ice deformation rates show an unexpected variation with depth that can be explained with the help of an ice-flow model as a consequence of stress transfer from slippery to sticky areas...

  18. Sulcal and gyral anatomy of the basal occipital-temporal lobe.

    Science.gov (United States)

    Chau, Anthony Minh Tien; Stewart, Fiona; Gragnaniello, Cristian

    2014-12-01

    The sulcal and gyral anatomy of the basal occipital-temporal lobe is highly variable and detailed descriptions of this region are limited and often inconsistent. The aim of this study was to describe the salient features of the sulcal and gyral anatomy of the basal occipital-temporal lobe. We studied the sulcal and gyral patterns of 30 formalin-fixed cerebral hemispheres. The major landmarks are the collateral sulcus (separated into the rhinal, proper, and caudal segments) and occipitotemporal sulcus (often interrupted), which were always present in this study. The bifurcation of the caudal collateral sulcus is a useful landmark. In relation to these sulci, we have described the surface anatomy and nominated landmarks of the medial (parahippocampal and lingual) and lateral (fusiform) occipitotemporal gyri. Understanding of the sulcal and gyral patterns of the basal occipital-temporal lobe may provide valuable information in its radiological and intraoperative interpretation.

  19. The molecular basis of the genesis of basal tone in internal anal sphincter

    Science.gov (United States)

    Zhang, Cheng-Hai; Wang, Pei; Liu, Dong-Hai; Chen, Cai-Ping; Zhao, Wei; Chen, Xin; Chen, Chen; He, Wei-Qi; Qiao, Yan-Ning; Tao, Tao; Sun, Jie; Peng, Ya-Jing; Lu, Ping; Zheng, Kaizhi; Craige, Siobhan M.; Lifshitz, Lawrence M.; Keaney Jr, John F.; Fogarty, Kevin E.; ZhuGe, Ronghua; Zhu, Min-Sheng

    2016-01-01

    Smooth muscle sphincters exhibit basal tone and control passage of contents through organs such as the gastrointestinal tract; loss of this tone leads to disorders such as faecal incontinence. However, the molecular mechanisms underlying this tone remain unknown. Here, we show that deletion of myosin light-chain kinases (MLCK) in the smooth muscle cells from internal anal sphincter (IAS-SMCs) abolishes basal tone, impairing defecation. Pharmacological regulation of ryanodine receptors (RyRs), L-type voltage-dependent Ca2+ channels (VDCCs) or TMEM16A Ca2+-activated Cl− channels significantly changes global cytosolic Ca2+ concentration ([Ca2+]i) and the tone. TMEM16A deletion in IAS-SMCs abolishes the effects of modulators for TMEM16A or VDCCs on a RyR-mediated rise in global [Ca2+]i and impairs the tone and defecation. Hence, MLCK activation in IAS-SMCs caused by a global rise in [Ca2+]i via a RyR-TMEM16A-VDCC signalling module sets the basal tone. Targeting this module may lead to new treatments for diseases like faecal incontinence. PMID:27101932

  20. Attenuated frontal and sensory inputs to the basal ganglia in cannabis users.

    Science.gov (United States)

    Blanco-Hinojo, Laura; Pujol, Jesus; Harrison, Ben J; Macià, Dídac; Batalla, Albert; Nogué, Santiago; Torrens, Marta; Farré, Magí; Deus, Joan; Martín-Santos, Rocío

    2017-07-01

    Heavy cannabis use is associated with reduced motivation. The basal ganglia, central in the motivation system, have the brain's highest cannabinoid receptor density. The frontal lobe is functionally coupled to the basal ganglia via segregated frontal-subcortical circuits conveying information from internal, self-generated activity. The basal ganglia, however, receive additional influence from the sensory system to further modulate purposeful behaviors according to the context. We postulated that cannabis use would impact functional connectivity between the basal ganglia and both internal (frontal cortex) and external (sensory cortices) sources of influence. Resting-state functional connectivity was measured in 28 chronic cannabis users and 29 controls. Selected behavioral tests included reaction time, verbal fluency and exposition to affective pictures. Assessments were repeated after one month of abstinence. Cannabis exposure was associated with (1) attenuation of the positive correlation between the striatum and areas pertaining to the 'limbic' frontal-basal ganglia circuit, and (2) attenuation of the negative correlation between the striatum and the fusiform gyrus, which is critical in recognizing significant visual features. Connectivity alterations were associated with lower arousal in response to affective pictures. Functional connectivity changes had a tendency to normalize after abstinence. The results overall indicate that frontal and sensory inputs to the basal ganglia are attenuated after chronic exposure to cannabis. This effect is consistent with the common behavioral consequences of chronic cannabis use concerning diminished responsiveness to both internal and external motivation signals. Such an impairment of the fine-tuning in the motivation system notably reverts after abstinence. © 2016 Society for the Study of Addiction.

  1. Basal aurora kinase B activity is sufficient for histone H3 phosphorylation in prophase

    Directory of Open Access Journals (Sweden)

    Ly-Thuy-Tram Le

    2013-02-01

    Histone H3 phosphorylation is the hallmark of mitosis deposited by aurora kinase B. Benzo[e]pyridoindoles are a family of potent, broad, ATP-competitive aurora kinase inhibitors. However, benzo[e]pyridoindole C4 only inhibits histone H3 phosphorylation in prophase but not in metaphase. Under the C4 treatment, the cells enter into mitosis with dephosphorylated histone H3, assemble chromosomes normally and progress to metaphase, and then to anaphase. C4 also induces lagging chromosome in anaphase but we demonstrated that these chromosome compaction defects are not related to the absence of H3 phosphorylation in prophase. As a result of C4 action, mitosis lasts longer and the cell cycle is slowed down. We reproduced the mitotic defects with reduced concentrations of potent pan aurora kinase as well as with a specific aurora B ATP-competitive inhibitor; we therefore propose that histone H3 phosphorylation and anaphase chromosome compaction involve the basal activity of aurora kinase B. Our data suggest that aurora kinase B is progressively activated at mitosis entry and at anaphase onset. The full activation of aurora kinase B by its partners, in prometaphase, induces a shift in the catalytic domain of aurora B that modifies its affinity for ATP. These waves of activation/deactivation of aurora B correspond to different conformations of the chromosomal complex revealed by FRAP. The presence of lagging chromosomes may have deleterious consequences on the daughter cells and, unfortunately, the situation may be encountered in patients receiving treatment with aurora kinase inhibitors.

  2. Phylogenetic differences of mammalian basal metabolic rate are not explained by mitochondrial basal proton leak.

    Science.gov (United States)

    Polymeropoulos, E T; Heldmaier, G; Frappell, P B; McAllan, B M; Withers, K W; Klingenspor, M; White, C R; Jastroch, M

    2012-01-07

    Metabolic rates of mammals presumably increased during the evolution of endothermy, but molecular and cellular mechanisms underlying basal metabolic rate (BMR) are still not understood. It has been established that mitochondrial basal proton leak contributes significantly to BMR. Comparative studies among a diversity of eutherian mammals showed that BMR correlates with body mass and proton leak. Here, we studied BMR and mitochondrial basal proton leak in liver of various marsupial species. Surprisingly, we found that the mitochondrial proton leak was greater in marsupials than in eutherians, although marsupials have lower BMRs. To verify our finding, we kept similar-sized individuals of a marsupial opossum (Monodelphis domestica) and a eutherian rodent (Mesocricetus auratus) species under identical conditions, and directly compared BMR and basal proton leak. We confirmed an approximately 40 per cent lower mass specific BMR in the opossum although its proton leak was significantly higher (approx. 60%). We demonstrate that the increase in BMR during eutherian evolution is not based on a general increase in the mitochondrial proton leak, although there is a similar allometric relationship of proton leak and BMR within mammalian groups. The difference in proton leak between endothermic groups may assist in elucidating distinct metabolic and habitat requirements that have evolved during mammalian divergence.

  3. Inter regional correlations of glucose metabolism between the basal ganglia and different cortical areas: an ultra-high resolution PET/MRI fusion study using {sup 18}F-FDG

    Energy Technology Data Exchange (ETDEWEB)

    Kim, J.H. [Research Institute for Advanced Industrial Technology, Korea University, Sejong (Korea, Republic of); Son, Y.D.; Kim, H.K.; Oh, C.H., E-mail: ohch@korea.ac.kr [College of Health Science, Gachon University, Incheon, (Korea, Republic of); Kim, J.M. [College of Science and Technology, Korea University, Sejong (Korea, Republic of); Kim, Y.B. [Gachon University School of Medicine, Incheon (Korea, Republic of); Lee, C. [Bioimaging Research Team, Korea Basic Science Institute, Cheongju (Korea, Republic of)

    2018-02-01

    Basal ganglia have complex functional connections with the cerebral cortex and are involved in motor control, executive functions of the forebrain, such as the planning of movement, and cognitive behaviors based on their connections. The aim of this study was to provide detailed functional correlation patterns between the basal ganglia and cerebral cortex by conducting an inter regional correlation analysis of the {sup 18}F-fluorodeoxyglucose ({sup 18}F-FDG) positron emission tomography (PET) data based on precise structural information. Fifteen participants were scanned with 7-Tesla magnetic resonance imaging (MRI) and high resolution research tomography (HRRT)-PET fusion system using {sup 18}F-FDG. For detailed inter regional correlation analysis, 24 subregions of the basal ganglia including pre-commissural dorsal caudate, post-commissural caudate, pre-commissural dorsal putamen, post-commissural putamen, internal globus pallidus, and external globus pallidus and 80 cerebral regions were selected as regions of interest on the MRI image and their glucose metabolism were calculated from the PET images. Pearson's product-moment correlation analysis was conducted for the inter regional correlation analysis of the basal ganglia. Functional correlation patterns between the basal ganglia and cerebral cortex were not only consistent with the findings of previous studies, but also showed new functional correlation between the dorsal striatum (i.e., caudate nucleus and putamen) and insula. In this study, we established the detailed basal ganglia subregional functional correlation patterns using {sup 18}F-FDG PET/MRI fusion imaging. Our methods and results could potentially be an important resource for investigating basal ganglia dysfunction as well as for conducting functional studies in the context of movement and psychiatric disorders. (author)

  4. Basal ganglia, movement disorders and deep brain stimulation: advances made through non-human primate research.

    Science.gov (United States)

    Wichmann, Thomas; Bergman, Hagai; DeLong, Mahlon R

    2018-03-01

    Studies in non-human primates (NHPs) have led to major advances in our understanding of the function of the basal ganglia and of the pathophysiologic mechanisms of hypokinetic movement disorders such as Parkinson's disease and hyperkinetic disorders such as chorea and dystonia. Since the brains of NHPs are anatomically very close to those of humans, disease states and the effects of medical and surgical approaches, such as deep brain stimulation (DBS), can be more faithfully modeled in NHPs than in other species. According to the current model of the basal ganglia circuitry, which was strongly influenced by studies in NHPs, the basal ganglia are viewed as components of segregated networks that emanate from specific cortical areas, traverse the basal ganglia, and ventral thalamus, and return to the frontal cortex. Based on the presumed functional domains of the different cortical areas involved, these networks are designated as 'motor', 'oculomotor', 'associative' and 'limbic' circuits. The functions of these networks are strongly modulated by the release of dopamine in the striatum. Striatal dopamine release alters the activity of striatal projection neurons which, in turn, influences the (inhibitory) basal ganglia output. In parkinsonism, the loss of striatal dopamine results in the emergence of oscillatory burst patterns of firing of basal ganglia output neurons, increased synchrony of the discharge of neighboring basal ganglia neurons, and an overall increase in basal ganglia output. The relevance of these findings is supported by the demonstration, in NHP models of parkinsonism, of the antiparkinsonian effects of inactivation of the motor circuit at the level of the subthalamic nucleus, one of the major components of the basal ganglia. This finding also contributed strongly to the revival of the use of surgical interventions to treat patients with Parkinson's disease. While ablative procedures were first used for this purpose, they have now been largely

  5. Distinct Temporal Coordination of Spontaneous Population Activity between Basal Forebrain and Auditory Cortex

    Directory of Open Access Journals (Sweden)

    Josue G. Yague

    2017-09-01

    Full Text Available The basal forebrain (BF has long been implicated in attention, learning and memory, and recent studies have established a causal relationship between artificial BF activation and arousal. However, neural ensemble dynamics in the BF still remains unclear. Here, recording neural population activity in the BF and comparing it with simultaneously recorded cortical population under both anesthetized and unanesthetized conditions, we investigate the difference in the structure of spontaneous population activity between the BF and the auditory cortex (AC in mice. The AC neuronal population show a skewed spike rate distribution, a higher proportion of short (≤80 ms inter-spike intervals (ISIs and a rich repertoire of rhythmic firing across frequencies. Although the distribution of spontaneous firing rate in the BF is also skewed, a proportion of short ISIs can be explained by a Poisson model at short time scales (≤20 ms and spike count correlations are lower compared to AC cells, with optogenetically identified cholinergic cell pairs showing exceptionally higher correlations. Furthermore, a smaller fraction of BF neurons shows spike-field entrainment across frequencies: a subset of BF neurons fire rhythmically at slow (≤6 Hz frequencies, with varied phase preferences to ongoing field potentials, in contrast to a consistent phase preference of AC populations. Firing of these slow rhythmic BF cells is correlated to a greater degree than other rhythmic BF cell pairs. Overall, the fundamental difference in the structure of population activity between the AC and BF is their temporal coordination, in particular their operational timescales. These results suggest that BF neurons slowly modulate downstream populations whereas cortical circuits transmit signals on multiple timescales. Thus, the characterization of the neural ensemble dynamics in the BF provides further insight into the neural mechanisms, by which brain states are regulated.

  6. The Evaluation of Basal Respiration for Various Soil Textures in Ecologically Sensitive Area

    Science.gov (United States)

    Huličová, P.; Kotorová, D.; Fazekašová, D.; Hynšt, J.

    2017-10-01

    The present contribution was focused on monitoring changes in the soil basal respiration in different textures of soil in the dry polder Beša. The research was conducted between 2012 and 2014 on soil type Fluvisol locations on three soil textures: clay - loam soil, clayey soil and clay soil in three soil depths. The basal respiration (BR) has been determine by soil CO2 production measuring from incubated soil samples in serum bottles in laboratory condition. Release Co2 has been analysed by gas chromatography. Content of clay particles were in the range 52.18 % to 81.31%, indicating the high difference between the minimum and maximum content. By using of multiple LSD-test we recorded statistically significant impact of clay on basal respiration. Results confirm the values of basal respiration with the depth of the soil profile decreased.

  7. Nevoid basal cell carcinoma syndrome (Gorlin-Goltz syndrome).

    Science.gov (United States)

    Kiran, N K; Tilak Raj, T N; Mukunda, K S; Rajashekar Reddy, V

    2012-10-01

    The Gorlin-Goltz syndrome, also known as nevoid basal cell carcinoma syndrome (NBCCS), is an infrequent multisystemic disease inherited in a dominant autosomal way, which shows a high level of penetrance and variable expressiveness. It is characterized by odontogenic keratocysts in the jaw, multiple basal cell nevi carcinomas and skeletal abnormalities. This syndrome may be diagnosed early by a dentist by routine radiographic exams in the first decade of life, since the odontogenic keratocysts are usually one of the first manifestations of the syndrome. This case report presents a patient diagnosed as NBCCS by clinical, radiographic and histological findings in a 13-year-old boy. This paper highlights the importance of early diagnosis of NBCCS which can help in preventive multidisciplinary approach to provide a better prognosis for the patient.

  8. Nevoid basal cell carcinoma syndrome (Gorlin-Goltz syndrome

    Directory of Open Access Journals (Sweden)

    N K Kiran

    2012-01-01

    Full Text Available The Gorlin-Goltz syndrome, also known as nevoid basal cell carcinoma syndrome (NBCCS, is an infrequent multisystemic disease inherited in a dominant autosomal way, which shows a high level of penetrance and variable expressiveness. It is characterized by odontogenic keratocysts in the jaw, multiple basal cell nevi carcinomas and skeletal abnormalities. This syndrome may be diagnosed early by a dentist by routine radiographic exams in the first decade of life, since the odontogenic keratocysts are usually one of the first manifestations of the syndrome. This case report presents a patient diagnosed as NBCCS by clinical, radiographic and histological findings in a 13-year-old boy. This paper highlights the importance of early diagnosis of NBCCS which can help in preventive multidisciplinary approach to provide a better prognosis for the patient.

  9. Sonic hedgehog-expressing basal cells are general post-mitotic precursors of functional taste receptor cells

    Science.gov (United States)

    Miura, Hirohito; Scott, Jennifer K.; Harada, Shuitsu; Barlow, Linda A.

    2014-01-01

    Background Taste buds contain ~60 elongate cells and several basal cells. Elongate cells comprise three functional taste cell types: I - glial cells, II - bitter/sweet/umami receptor cells, and III - sour detectors. Although taste cells are continuously renewed, lineage relationships among cell types are ill-defined. Basal cells have been proposed as taste bud stem cells, a subset of which express Sonic hedgehog (Shh). However, Shh+ basal cells turnover rapidly suggesting that Shh+ cells are precursors of some or all taste cell types. Results To fate map Shh-expressing cells, mice carrying ShhCreERT2 and a high (CAG-CAT-EGFP) or low (R26RLacZ) efficiency reporter allele were given tamoxifen to activate Cre in Shh+ cells. Using R26RLacZ, lineage-labeled cells occur singly within buds, supporting a post-mitotic state for Shh+ cells. Using either reporter, we show that Shh+ cells differentiate into all three taste cell types, in proportions reflecting cell type ratios in taste buds (I > II > III). Conclusions Shh+ cells are not stem cells, but are post-mitotic, immediate precursors of taste cells. Shh+ cells differentiate into each of the three taste cell types, and the choice of a specific taste cell fate is regulated to maintain the proper ratio within buds. PMID:24590958

  10. The contribution of ketone bodies to basal and activity-dependent neuronal oxidation in vivo.

    Science.gov (United States)

    Chowdhury, Golam M I; Jiang, Lihong; Rothman, Douglas L; Behar, Kevin L

    2014-07-01

    The capacity of ketone bodies to replace glucose in support of neuronal function is unresolved. Here, we determined the contributions of glucose and ketone bodies to neocortical oxidative metabolism over a large range of brain activity in rats fasted 36 hours and infused intravenously with [2,4-(13)C₂]-D-β-hydroxybutyrate (BHB). Three animal groups and conditions were studied: awake ex vivo, pentobarbital-induced isoelectricity ex vivo, and halothane-anesthetized in vivo, the latter data reanalyzed from a recent study. Rates of neuronal acetyl-CoA oxidation from ketone bodies (V(acCoA-kbN)) and pyruvate (V(pdhN)), and the glutamate-glutamine cycle (V(cyc)) were determined by metabolic modeling of (13)C label trapped in major brain amino acid pools. V(acCoA-kbN) increased gradually with increasing activity, as compared with the steeper change in tricarboxylic acid (TCA) cycle rate (V(tcaN)), supporting a decreasing percentage of neuronal ketone oxidation: ∼100% (isoelectricity), 56% (halothane anesthesia), 36% (awake) with the BHB plasma levels achieved in our experiments (6 to 13 mM). In awake animals ketone oxidation reached saturation for blood levels >17 mM, accounting for 62% of neuronal substrate oxidation, the remainder (38%) provided by glucose. We conclude that ketone bodies present at sufficient concentration to saturate metabolism provides full support of basal (housekeeping) energy needs and up to approximately half of the activity-dependent oxidative needs of neurons.

  11. Loss of Dickkopf 3 Promotes the Tumorigenesis of Basal Breast Cancer.

    Directory of Open Access Journals (Sweden)

    Eva Lorsy

    Full Text Available Dickkopf 3 (DKK3 has been associated with tumor suppression of various tumor entities including breast cancer. However, the functional impact of DKK3 on the tumorigenesis of distinct molecular breast cancer subtypes has not been considered so far. Therefore, we initiated a study analyzing the subtype-specific DKK3 expression pattern as well as its prognostic and functional impact with respect to breast cancer subtypes. Based on three independent tissue cohorts including one in silico dataset (n = 30, n = 463 and n = 791 we observed a clear down-regulation of DKK3 expression in breast cancer samples compared to healthy breast tissue controls on mRNA and protein level. Interestingly, most abundant reduction of DKK3 expression was detected in the highly aggressive basal breast cancer subtype. Analyzing a large in silico dataset comprising 3,554 cases showed that low DKK3 mRNA expression was significantly associated with reduced recurrence free survival (RFS of luminal and basal-like breast cancer cases. Functionally, DKK3 re-expression in human breast cancer cell lines led to suppression of cell growth possibly mediated by up-regulation of apoptosis in basal-like but not in luminal-like breast cancer cell lines. Moreover, ectopic DKK3 expression in mesenchymal basal breast cancer cells resulted in partial restoration of epithelial cell morphology which was molecularly supported by higher expression of epithelial markers like E-Cadherin and down-regulation of mesenchymal markers such as Snail 1. Hence, we provide evidence that down-regulation of DKK3 especially promotes tumorigenesis of the aggressive basal breast cancer subtype. Further studies decoding the underlying molecular mechanisms of DKK3-mediated effects may help to identify novel targeted therapies for this clinically highly relevant breast cancer subtype.

  12. Functional impairments in patients with borderline personality disorders demonstrated by neurospect HMPAO Tc99 in basal conditions and under frontal activation

    International Nuclear Information System (INIS)

    Prado, Cristian; Mena G, Ismael; Correa, Maria del Pilar

    2000-01-01

    We study a sample of 18 patients in basal conditions and 31 patients with diagnosis of Borderline Personality Disorder (DSM-IV Criteria) during cortical activation by means of the Wisconsin card sorting test and assessing function/cerebral blood flow by means of HMPAO Tc 99m NeuroSPECT. The results of changes of cerebral blood flow are shown statistically in a parametric image expressing standard deviations above or below the means of a normative data base for the corresponding age of the patient. We consider only as having significance levels below 2 standard deviations of the normal means . Over this parametric map we project a matrix of Brodmann areas developed by our group in order to precisely localize the areas of abnormality observed. We express our results as percentages of the areas of Brodmann that demonstrates hypoperfusion and we compare the results in a population studied in basal conditions (n=18) and (n=31) during activation by means of the Wisconsin card sorting test. In our results we highlight, in order of importance areas of paradoxical hypoperfusion in conditions of activation versus basal measurements in anterior cyngulate gyrus (Area 24) in both hemispheres. This is followed in importance by Subgenual area (Area 25), area 40 and area 32 in the left hemisphere, and area 28 in the right hemisphere, then followed by area 28 and area 36 in the left hemisphere, area M* and area 44 in both hemispheres, and areas 32, 9 and 46 of Brodmann in the right hemisphere. We concluded that there is a dysfunctional correlation of frontal function in borderline personality disorder. Particularly noticeable is the lack of motivation when there are changes in plans and conduct, lack of pleasure and loss of the meaning of a task during the cortical stimulation. In particular, the Brodmann areas 24, 25 and 32, linked to motivation show a wider involvement when they are exposed to changes in planning and in coping strategies, as it happens during the Wisconsin Test

  13. Selective attentional enhancement and inhibition of fronto-posterior connectivity by the basal ganglia during attention switching.

    Science.gov (United States)

    van Schouwenburg, Martine R; den Ouden, Hanneke E M; Cools, Roshan

    2015-06-01

    The prefrontal cortex and the basal ganglia interact to selectively gate a desired action. Recent studies have shown that this selective gating mechanism of the basal ganglia extends to the domain of attention. Here, we investigate the nature of this action-like gating mechanism for attention using a spatial attention-switching paradigm in combination with functional neuroimaging and dynamic causal modeling. We show that the basal ganglia guide attention by focally releasing inhibition of task-relevant representations, while simultaneously inhibiting task-irrelevant representations by selectively modulating prefrontal top-down connections. These results strengthen and specify the role of the basal ganglia in attention. Moreover, our findings have implications for psychological theorizing by suggesting that inhibition of unattended sensory regions is not only a consequence of mutual suppression, but is an active process, subserved by the basal ganglia. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  14. The Distribution of Basal Water Beneath the Greenland Ice Sheet from Radio-Echo Sounding

    Science.gov (United States)

    Jordan, T.; Williams, C.; Schroeder, D. M.; Martos, Y. M.; Cooper, M.; Siegert, M. J.; Paden, J. D.; Huybrechts, P.; Bamber, J. L.

    2017-12-01

    There is widespread, but often indirect, evidence that a significant fraction of the Greenland Ice Sheet is thawed at the bed. This includes major outlet glaciers and around the NorthGRIP ice-core in the interior. However, the ice-sheet-wide distribution of basal water is poorly constrained by existing observations, and the spatial relationship between basal water and other ice-sheet and subglacial properties is therefore largely unexplored. In principle, airborne radio-echo sounding (RES) surveys provide the necessary information and spatial coverage to infer the presence of basal water at the ice-sheet scale. However, due to uncertainty and spatial variation in radar signal attenuation, the commonly used water diagnostic, bed-echo reflectivity, is highly ambiguous and prone to spatial bias. Here we introduce a new RES diagnostic for the presence of basal water which incorporates both sharp step-transitions and rapid fluctuations in bed-echo reflectivity. This has the advantage of being (near) independent of attenuation model, and enables a decade of recent Operation Ice Bride RES survey data to be combined in a single map for basal water. The ice-sheet-wide water predictions are compared with: bed topography and drainage network structure, existing knowledge of the thermal state and geothermal heat flux, and ice velocity. In addition to the fast flowing ice-sheet margins, we also demonstrate widespread water routing and storage in parts of the slow-flowing northern interior. Notably, this includes a quasi-linear `corridor' of basal water, extending from NorthGRIP to Petermann glacier, which spatially correlates with a region of locally high (magnetic-derived) geothermal heat flux. The predicted water distribution places a new constraint upon the basal thermal state of the Greenland Ice Sheet, and could be used as an input for ice-sheet model simulations.

  15. Basal ganglia calcification on CT in adult patients with Down's syndrome

    International Nuclear Information System (INIS)

    Ono, Yoshiro; Yoshida, Hironobu; Yoshimasu, Fumio; Higashi, Yuji.

    1987-01-01

    Fourteen adult cases with Down's syndrome were examined on cranial CT scan, and 5 of them (35.7 %) showed basal ganglia calcification (BGC). The incidence of BGC in the present cases was very high in comparison with the one in general population (0.3 ∼ 1.5 %). Abnormalities of calcium metabolism or dysfunctions of the basal ganglia were absent in each case with BGC. Calcifications were exclusively located in globus pallidus. It is considered that BGC found in the present cases may be due to the premature aging process in Down's syndrome. (author)

  16. Localized basal meningeal enhancement in tuberculous meningitis

    Energy Technology Data Exchange (ETDEWEB)

    Theron, Salomine; Andronikou, Savvas; Grobbelaar, Marie; Steyn, Freda; Mapukata, Ayanda; Plessis, Jaco du [University of Stellenbosch, Department of Radiology, Tygerberg Hospital, P.O. BOX 19063, Tygerberg (South Africa)

    2006-11-15

    Focal basal meningeal enhancement may produce a confusing CT picture in children with suspected tuberculous meningitis (TBM). To demonstrate the incidence, distribution and appearance of localized basal meningeal enhancement in children with TBM. CT scans of patients with definite (culture proven) and probable (CSF suggestive) TBM were retrospectively evaluated by two observers. Localized basal enhancement was documented as involving: unilateral cistern of the lateral fossa (CLF), unilateral sylvian fissure, unilateral CLF and sylvian fissure in combination, unilateral CLF and sylvian fissure with ipsi- or contralateral ambient cistern and isolated quadrigeminal plate cistern. The study included 130 patients with TBM (aged 2 months to 13 years 9 months). Focal basal enhancement was seen in 11 patients (8.5%). The sylvian fissure was involved most commonly, followed by the lateral fossa cistern. The ambient cistern was involved in three patients and the quadrigeminal plate cistern in one. Focal areas of enhancement corresponded to the areas of infarction in every patient. Focal basal meningeal enhancement is common (8.5%) in paediatric TBM. This must be kept in mind when evaluating CT scans in children presenting with focal neurological findings, seizures or meningism in communities where TBM is endemic. (orig.)

  17. Localized basal meningeal enhancement in tuberculous meningitis

    International Nuclear Information System (INIS)

    Theron, Salomine; Andronikou, Savvas; Grobbelaar, Marie; Steyn, Freda; Mapukata, Ayanda; Plessis, Jaco du

    2006-01-01

    Focal basal meningeal enhancement may produce a confusing CT picture in children with suspected tuberculous meningitis (TBM). To demonstrate the incidence, distribution and appearance of localized basal meningeal enhancement in children with TBM. CT scans of patients with definite (culture proven) and probable (CSF suggestive) TBM were retrospectively evaluated by two observers. Localized basal enhancement was documented as involving: unilateral cistern of the lateral fossa (CLF), unilateral sylvian fissure, unilateral CLF and sylvian fissure in combination, unilateral CLF and sylvian fissure with ipsi- or contralateral ambient cistern and isolated quadrigeminal plate cistern. The study included 130 patients with TBM (aged 2 months to 13 years 9 months). Focal basal enhancement was seen in 11 patients (8.5%). The sylvian fissure was involved most commonly, followed by the lateral fossa cistern. The ambient cistern was involved in three patients and the quadrigeminal plate cistern in one. Focal areas of enhancement corresponded to the areas of infarction in every patient. Focal basal meningeal enhancement is common (8.5%) in paediatric TBM. This must be kept in mind when evaluating CT scans in children presenting with focal neurological findings, seizures or meningism in communities where TBM is endemic. (orig.)

  18. Lesions of the basal forebrain cholinergic system in mice disrupt idiothetic navigation.

    Directory of Open Access Journals (Sweden)

    Adam S Hamlin

    Full Text Available Loss of integrity of the basal forebrain cholinergic neurons is a consistent feature of Alzheimer's disease, and measurement of basal forebrain degeneration by magnetic resonance imaging is emerging as a sensitive diagnostic marker for prodromal disease. It is also known that Alzheimer's disease patients perform poorly on both real space and computerized cued (allothetic or uncued (idiothetic recall navigation tasks. Although the hippocampus is required for allothetic navigation, lesions of this region only mildly affect idiothetic navigation. Here we tested the hypothesis that the cholinergic medial septo-hippocampal circuit is important for idiothetic navigation. Basal forebrain cholinergic neurons were selectively lesioned in mice using the toxin saporin conjugated to a basal forebrain cholinergic neuronal marker, the p75 neurotrophin receptor. Control animals were able to learn and remember spatial information when tested on a modified version of the passive place avoidance test where all extramaze cues were removed, and animals had to rely on idiothetic signals. However, the exploratory behaviour of mice with cholinergic basal forebrain lesions was highly disorganized during this test. By contrast, the lesioned animals performed no differently from controls in tasks involving contextual fear conditioning and spatial working memory (Y maze, and displayed no deficits in potentially confounding behaviours such as motor performance, anxiety, or disturbed sleep/wake cycles. These data suggest that the basal forebrain cholinergic system plays a specific role in idiothetic navigation, a modality that is impaired early in Alzheimer's disease.

  19. Detecting high spatial variability of ice shelf basal mass balance, Roi Baudouin Ice Shelf, Antarctica

    Directory of Open Access Journals (Sweden)

    S. Berger

    2017-11-01

    Full Text Available Ice shelves control the dynamic mass loss of ice sheets through buttressing and their integrity depends on the spatial variability of their basal mass balance (BMB, i.e. the difference between refreezing and melting. Here, we present an improved technique – based on satellite observations – to capture the small-scale variability in the BMB of ice shelves. As a case study, we apply the methodology to the Roi Baudouin Ice Shelf, Dronning Maud Land, East Antarctica, and derive its yearly averaged BMB at 10 m horizontal gridding. We use mass conservation in a Lagrangian framework based on high-resolution surface velocities, atmospheric-model surface mass balance and hydrostatic ice-thickness fields (derived from TanDEM-X surface elevation. Spatial derivatives are implemented using the total-variation differentiation, which preserves abrupt changes in flow velocities and their spatial gradients. Such changes may reflect a dynamic response to localized basal melting and should be included in the mass budget. Our BMB field exhibits much spatial detail and ranges from −14.7 to 8.6 m a−1 ice equivalent. Highest melt rates are found close to the grounding line where the pressure melting point is high, and the ice shelf slope is steep. The BMB field agrees well with on-site measurements from phase-sensitive radar, although independent radar profiling indicates unresolved spatial variations in firn density. We show that an elliptical surface depression (10 m deep and with an extent of 0.7 km × 1.3 km lowers by 0.5 to 1.4 m a−1, which we tentatively attribute to a transient adaptation to hydrostatic equilibrium. We find evidence for elevated melting beneath ice shelf channels (with melting being concentrated on the channel's flanks. However, farther downstream from the grounding line, the majority of ice shelf channels advect passively (i.e. no melting nor refreezing toward the ice shelf front. Although the absolute, satellite

  20. Red Dot Basal Cell Carcinoma: An Unusual Variant of a Common Malignancy.

    Science.gov (United States)

    Loh, Tiffany Y; Cohen, Philip R

    2016-05-01

    Red dot basal cell carcinoma is a distinct but rare subtype of basal cell carcinoma (BCC). It presents as a red macule or papule; therefore, in most cases, it may easily be mistaken for a benign vascular lesion, such as a telangiectasia or angioma. A red dot BCC in an older woman is described. Clinical and histological differences between red dot BCCs and telangiectasias are described. A 72-year-old woman initially presented with a painless red macule on her nose. Biopsy of the lesion established the diagnosis of a red dot BCC. Pubmed was searched for the following terms: angioma, basal cell carcinoma, dermoscope, diascopy, red dot, non-melanoma skin cancer, telangiectasia, and vascular. The papers were reviewed for cases of red dot basal cell carcinoma. Clinical and histological characteristics of red dot basal cell carcinoma and telangiectasias were compared. Red dot BCC is an extremely rare variant of BCC that may be confused with benign vascular lesions. Although BCCs rarely metastasize and are associated with low mortality, they have the potential to become locally invasive and destructive if left untreated. Thus, a high index of suspicion for red dot BCC is necessary. J Drugs Dermatol. 2016;15(5):645-647.

  1. A Classic Case of Basal Cell Nevus Syndrome

    Directory of Open Access Journals (Sweden)

    Dattaprasad Dadhe

    2015-01-01

    Full Text Available The basal cell nevus syndrome is an autosomal dominant inherited condition characterized mainly by basal cell carcinomas, multiple keratinizing odontogenic tumors, and other systemic anomalies. As these manifestations do not alter the patient′s lifestyle, most of the cases are diagnosed through oral abnormalities. A classic case of basal cell nevus syndrome fulfilling almost all the major and minor criteria has been reported here.

  2. Triple-negative breast cancer with brain metastases: a comparison between basal-like and non-basal-like biological subtypes

    NARCIS (Netherlands)

    A. Niwińska (Anna); W. Olszewski (Wojciech); M. Murawska (Magdalena); K. Pogoda (Katarzyna)

    2011-01-01

    textabstractThe aim of this study was to divide the group of triple-negative breast cancer patients with brain metastases into basal-like and non-basal-like biological subtypes in order to compare clinical features and survival rates in those two groups. A comprehensive analysis of 111 consecutive

  3. Basal Cell Carcinoma Arising in a Tattooed Eyebrow

    Science.gov (United States)

    Lee, Jong-Sun; Park, Jin; Kim, Seong-Min; Kim, Han-Uk

    2009-01-01

    Malignant skin tumors, including squamous cell carcinoma and malignant melanoma, have occurred in tattoos. Seven documented cases of basal cell carcinoma associated with tattoos have also been reported in the medical literature. We encountered a patient with basal cell carcinoma in a tattooed eyebrow. We report on this case as the eighth reported case of a patient with basal cell carcinoma arising in a tattooed area. PMID:20523804

  4. Chronological changes in nonhaemorrhagic brain infarcts with short T1 in the cerebellum and basal ganglia

    Energy Technology Data Exchange (ETDEWEB)

    Komiyama, M.; Nakajima, H.; Nishikawa, M.; Yasui, T. [Dept. of Neurosurgery, Osaka City General Hospital, Miyakojima-Hondouri, Miyakojima, Osaka (Japan)

    2000-07-01

    Our purpose was to investigate nonhaemorrhagic infarcts with a short T1 in the cerebellum and basal ganglia. We carried out repeat MRI on 12 patients with infarcts in the cerebellum or basal ganglia with a short T1. Cerebellar cortical lesions showed high signal on T1-weighted spin-echo images beginning at 2 weeks, which became prominent from 3 weeks to 2 months, and persisted for as long as 14 months after the ictus. The basal ganglia lesions demonstrated slightly high signal from a week after the ictus, which became more intense thereafter. Signal intensity began to fade gradually after 2 months. High signal could be seen at the periphery until 5 months, and then disappeared, while low or isointense signal, seen in the central portion from day 20, persisted thereafter. (orig.)

  5. Chronological changes in nonhaemorrhagic brain infarcts with short T1 in the cerebellum and basal ganglia

    International Nuclear Information System (INIS)

    Komiyama, M.; Nakajima, H.; Nishikawa, M.; Yasui, T.

    2000-01-01

    Our purpose was to investigate nonhaemorrhagic infarcts with a short T1 in the cerebellum and basal ganglia. We carried out repeat MRI on 12 patients with infarcts in the cerebellum or basal ganglia with a short T1. Cerebellar cortical lesions showed high signal on T1-weighted spin-echo images beginning at 2 weeks, which became prominent from 3 weeks to 2 months, and persisted for as long as 14 months after the ictus. The basal ganglia lesions demonstrated slightly high signal from a week after the ictus, which became more intense thereafter. Signal intensity began to fade gradually after 2 months. High signal could be seen at the periphery until 5 months, and then disappeared, while low or isointense signal, seen in the central portion from day 20, persisted thereafter. (orig.)

  6. Germinoma originating in the basal ganglia

    International Nuclear Information System (INIS)

    Anno, Y.; Hori, T.; Watanabe, T.; Takenobu, A.; Takigawa, H.; Kishimoto, M.; Tanaka, J.

    1990-01-01

    About 5-10% of primary intracranial germ cell tumors arise in basal ganglia and thalamus, where CT studies have been made. MR of the tumors in the pineal region, and to our knowledge, from one tumor in the basal ganglia were similar. In the present case, MR produced confusion in confirming diagnosis, which may require additional evidence from the clinical course, tumor markers, and CT images. (orig.)

  7. Dynamics of action potential backpropagation in basal dendrites of prefrontal cortical pyramidal neurons.

    Science.gov (United States)

    Zhou, Wen-Liang; Yan, Ping; Wuskell, Joseph P; Loew, Leslie M; Antic, Srdjan D

    2008-02-01

    Basal dendrites of neocortical pyramidal neurons are relatively short and directly attached to the cell body. This allows electrical signals arising in basal dendrites to strongly influence the neuronal output. Likewise, somatic action potentials (APs) should readily propagate back into the basilar dendritic tree to influence synaptic plasticity. Two recent studies, however, determined that sodium APs are severely attenuated in basal dendrites of cortical pyramidal cells, so that they completely fail in distal dendritic segments. Here we used the latest improvements in the voltage-sensitive dye imaging technique (Zhou et al., 2007) to study AP backpropagation in basal dendrites of layer 5 pyramidal neurons of the rat prefrontal cortex. With a signal-to-noise ratio of > 15 and minimal temporal averaging (only four sweeps) we were able to sample AP waveforms from the very last segments of individual dendritic branches (dendritic tips). We found that in short- (< 150 microm) and medium (150-200 microm in length)-range basal dendrites APs backpropagated with modest changes in AP half-width or AP rise-time. The lack of substantial changes in AP shape and dynamics of rise is inconsistent with the AP-failure model. The lack of substantial amplitude boosting of the third AP in the high-frequency burst also suggests that in short- and medium-range basal dendrites backpropagating APs were not severely attenuated. Our results show that the AP-failure concept does not apply in all basal dendrites of the rat prefrontal cortex. The majority of synaptic contacts in the basilar dendritic tree actually received significant AP-associated electrical and calcium transients.

  8. Basal Cell Ameloblastoma: A Rare Histological Variant of an ...

    African Journals Online (AJOL)

    Ameloblastomas are an inscrutable group of oral tumors. Basal cell ameloblastoma is a rare variant of ameloblastoma with very few cases reported until date. The tumor is composed of more primitive cells and has less conspicuous peripheral palisading. It shows remarkable similarity to basal cell carcinoma, basal cell ...

  9. Availability of the basal planes of graphene oxide determines whether it is antibacterial.

    Science.gov (United States)

    Hui, Liwei; Piao, Ji-Gang; Auletta, Jeffrey; Hu, Kan; Zhu, Yanwu; Meyer, Tara; Liu, Haitao; Yang, Lihua

    2014-08-13

    There are significant controversies on the antibacterial properties of graphene oxide (GO): GO was reported to be bactericidal in saline, whereas its activity in nutrient broth was controversial. To unveil the mechanisms underlying these contradictions, we performed antibacterial assays under comparable conditions. In saline, bare GO sheets were intrinsically bactericidal, yielding a bacterial survival percentage of planes. Using bovine serum albumin and tryptophan as well-defined model adsorbates, we found that noncovalent adsorption on GO basal planes may account for the deactivation of GO's bactericidal activity. Moreover, this deactivation mechanism was shown to be extrapolatable to GO's cytotoxicity against mammalian cells. Taken together, our observations suggest that bare GO intrinsically kills both bacteria and mammalian cells and noncovalent adsorption on its basal planes may be a global deactivation mechanism for GO's cytotoxicity.

  10. RhoA/ROCK pathway is the major molecular determinant of basal tone in intact human internal anal sphincter.

    Science.gov (United States)

    Rattan, Satish; Singh, Jagmohan

    2012-04-01

    The knowledge of molecular control mechanisms underlying the basal tone in the intact human internal anal sphincter (IAS) is critical for the pathophysiology and rational therapy for a number of debilitating rectoanal motility disorders. We determined the role of RhoA/ROCK and PKC pathways by comparing the effects of ROCK- and PKC-selective inhibitors Y 27632 and Gö 6850 (10(-8) to 10(-4) M), respectively, on the basal tone in the IAS vs. the rectal smooth muscle (RSM). Western blot studies were performed to determine the levels of RhoA/ROCK II, PKC-α, MYPT1, CPI-17, and MLC(20) in the unphosphorylated and phosphorylated forms, in the IAS vs. RSM. Confocal microscopic studies validated the membrane distribution of ROCK II. Finally, to confirm a direct relationship, we examined the enzymatic activities and changes in the basal IAS tone and p-MYPT1, p-CPI-17, and p-MLC(20), before and after Y 27632 and Gö 6850. Data show higher levels of RhoA/ROCK II and related downstream signal transduction proteins in the IAS vs. RSM. In addition, data show a significant correlation between the active RhoA/ROCK levels, ROCK enzymatic activity, downstream proteins, and basal IAS tone, before and after ROCK inhibitor. From these data we conclude 1) RhoA/ROCK and downstream signaling are constitutively active in the IAS, and this pathway (in contrast with PKC) is the critical determinant of the basal tone in intact human IAS; and 2) RhoA and ROCK are potential therapeutic targets for a number of rectoanal motility disorders for which currently there is no satisfactory treatment.

  11. Degludec insulin: A novel basal insulin

    OpenAIRE

    Kalra, Sanjay; Unnikrishnan, Ambika Gopalakrishnan; Baruah, Manash; Kalra, Bharti

    2011-01-01

    This paper reviews a novel insulin analogue, degludec, which has the potential to emerge as an ideal basal insulin. It reviews the limitations of existing basal insulin and analogues, and highlights the need for a newer molecule. The paper discusses the potential advantages of degludec, while reviewing its pharmacologic and clinical studies done so far. The paper assesses the potential role of insulin degludec and degludec plus in clinical diabetes practice.

  12. Instruction of Research-Based Comprehension Strategies in Basal Reading Programs

    Science.gov (United States)

    Pilonieta, Paola

    2010-01-01

    Research supports using research-based comprehension strategies; however, comprehension strategy instruction is not highly visible in basal reading programs or classroom instruction, resulting in many students who struggle with comprehension. A content analysis examined which research-based comprehension strategies were presented in five…

  13. Will the next generation of basal insulins offer clinical advantages?

    Science.gov (United States)

    Garber, A J

    2014-06-01

    The 21st century has seen the arrival of several insulin analogue products and the refinement of insulin regimens, with widespread advocacy of continuous titration algorithms and earlier initiation of supplementary insulin therapy (predominantly using basal insulins) in type 2 diabetes. Nevertheless, many insulin-treated diabetes patients remain in poor glycaemic control. This might reflect insufficient titration effort or lax adherence, but these issues could in some cases result from concerns about hypoglycaemia. Certainly there is scope for improving the pharmacokinetic/pharmacodynamic (PK/PD) profile of basal insulin, and three new products offer this prospect. Insulin degludec, now in clinical use, and PEGylated insulin lispro, in development, have greatly extended action profiles that result from two very different, but unique, mechanisms. With once-daily dosing, these insulins produce stable PK/PD profiles at steady state, associated with a low incidence of hypoglycaemia. The feasibility of varied daily dose timing has also been confirmed with insulin degludec. High strength formulations of insulin glargine and insulin degludec offer the prospect of a reduced injection number/volume in high dose users, and in the case of glargine, the PK/PD profile might also be favourably modified. This review considers critically the clinical evidence and expectations we should have for these new basal insulins. © 2013 John Wiley & Sons Ltd.

  14. Organizational changes of the daughter basal complex during the parasite replication of Toxoplasma gondii.

    Directory of Open Access Journals (Sweden)

    Ke Hu

    2008-01-01

    Full Text Available The apicomplexans are a large group of parasitic protozoa, many of which are important human and animal pathogens, including Plasmodium falciparum and Toxoplasma gondii. These parasites cause disease only when they replicate, and their replication is critically dependent on the proper assembly of the parasite cytoskeletons during cell division. In addition to their importance in pathogenesis, the apicomplexan parasite cytoskeletons are spectacular structures. Therefore, understanding the cytoskeletal biogenesis of these parasites is important not only for parasitology but also of general interest to broader cell biology. Previously, we found that the basal end of T. gondii contains a novel cytoskeletal assembly, the basal complex, a cytoskeletal compartment constructed in concert with the daughter cortical cytoskeleton during cell division. This study focuses on key events during the biogenesis of the basal complex using high resolution light microscopy, and reveals that daughter basal complexes are established around the duplicated centrioles independently of the structural integrity of the daughter cortical cytoskeleton, and that they are dynamic "caps" at the growing ends of the daughters. Compartmentation and polarization of the basal complex is first revealed at a late stage of cell division upon the recruitment of an EF-hand containing calcium binding protein, TgCentrin2. This correlates with the constriction of the basal complex, a process that can be artificially induced by increasing cellular calcium concentration. The basal complex is therefore likely to be a new kind of centrin-based contractile apparatus.

  15. Protein profile of basal prostate epithelial progenitor cells--stage-specific embryonal antigen 4 expressing cells have enhanced regenerative potential in vivo.

    Science.gov (United States)

    Höfner, Thomas; Klein, Corinna; Eisen, Christian; Rigo-Watermeier, Teresa; Haferkamp, Axel; Sprick, Martin R

    2016-04-01

    The long-term propagation of basal prostate progenitor cells ex vivo has been very difficult in the past. The development of novel methods to expand prostate progenitor cells in vitro allows determining their cell surface phenotype in greater detail. Mouse (Lin(-)Sca-1(+) CD49f(+) Trop2(high)-phenotype) and human (Lin(-) CD49f(+) TROP2(high)) basal prostate progenitor cells were expanded in vitro. Human and mouse cells were screened using 242 anti-human or 176 antimouse monoclonal antibodies recognizing the cell surface protein profile. Quantitative expression was evaluated at the single-cell level using flow cytometry. Differentially expressed cell surface proteins were evaluated in conjunction with the known CD49f(+)/TROP2(high) phenotype of basal prostate progenitor cells and characterized by in vivo sandwich-transplantation experiments using nude mice. The phenotype of basal prostate progenitor cells was determined as CD9(+)/CD24(+)/CD29(+)/CD44(+)/CD47(+)/CD49f(+)/CD104(+)/CD147(+)/CD326(+)/Trop2(high) of mouse as well as human origin. Our analysis revealed several proteins, such as CD13, Syndecan-1 and stage-specific embryonal antigens (SSEAs), as being differentially expressed on murine and human CD49f(+) TROP2(+) basal prostate progenitor cells. Transplantation experiments suggest that CD49f(+) TROP2(high) SSEA-4(high) human prostate basal progenitor cells to be more potent to regenerate prostate tubules in vivo as compared with CD49f(+) TROP2(high) or CD49f(+) TROP2(high) SSEA-4(low) cells. Determination of the cell surface protein profile of functionally defined murine and human basal prostate progenitor cells reveals differentially expressed proteins that may change the potency and regenerative function of epithelial progenitor cells within the prostate. SSEA-4 is a candidate cell surface marker that putatively enables a more accurate identification of the basal PESC lineage. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by

  16. The coupled response to slope-dependent basal melting

    Science.gov (United States)

    Little, C. M.; Goldberg, D. N.; Sergienko, O. V.; Gnanadesikan, A.

    2009-12-01

    Ice shelf basal melting is likely to be strongly controlled by basal slope. If ice shelves steepen in response to intensified melting, it suggests instability in the coupled ice-ocean system. The dynamic response of ice shelves governs what stable morphologies are possible, and thus the influence of melting on buttressing and grounding line migration. Simulations performed using a 3-D ocean model indicate that a simple form of slope-dependent melting is robust under more complex oceanographic conditions. Here we utilize this parameterization to investigate the shape and grounding line evolution of ice shelves, using a shallow-shelf approximation-based model that includes lateral drag. The distribution of melting substantially affects the shape and aspect ratio of unbuttressed ice shelves. Slope-dependent melting thins the ice shelf near the grounding line, reducing velocities throughout the shelf. Sharp ice thickness gradients evolve at high melting rates, yet grounding lines remain static. In foredeepened, buttressed ice shelves, changes in grounding line flux allow two additional options: stable or unstable retreat. Under some conditions, slope-dependent melting results in stable configurations even at high melt rates.

  17. Chronic Stress and Adolescents' Mental Health : Modifying Effects of Basal Cortisol and Parental Psychiatric History. The TRAILS Study

    NARCIS (Netherlands)

    Zandstra, Anna Roos E.; Hartman, Catharina A.; Nederhof, Esther; van den Heuvel, Edwin R.; Dietrich, Andrea; Hoekstra, Pieter J.; Ormel, Johan

    Large individual differences in adolescent mental health following chronic psychosocial stress suggest moderating factors. We examined two established moderators, basal cortisol and parental psychiatric history, simultaneously. We hypothesized that individuals with high basal cortisol, assumed to

  18. Toward sophisiticated basal ganglia neuromodulation: review on basal gaglia deep brain stimulation

    Science.gov (United States)

    Da Cunha, Claudio; Boschen, Suelen L.; Gómez-A, Alexander; Ross, Erika K.; Gibson, William S. J.; Min, Hoon-Ki; Lee, Kendall H.; Blaha, Charles D.

    2015-01-01

    This review presents state-of-the-art knowledge about the roles of the basal ganglia (BG) in action-selection, cognition, and motivation, and how this knowledge has been used to improve deep brain stimulation (DBS) treatment of neurological and psychiatric disorders. Such pathological conditions include Parkinson’s disease, Huntington’s disease, Tourette syndrome, depression, and obsessive-compulsive disorder. The first section presents evidence supporting current hypotheses of how the cortico-BG circuitry works to select motor and emotional actions, and how defects in this circuitry can cause symptoms of the BG diseases. Emphasis is given to the role of striatal dopamine on motor performance, motivated behaviors and learning of procedural memories. Next, the use of cutting-edge electrochemical techniques in animal and human studies of BG functioning under normal and disease conditions is discussed. Finally, functional neuroimaging studies are reviewed; these works have shown the relationship between cortico-BG structures activated during DBS and improvement of disease symptoms. PMID:25684727

  19. Toward sophisticated basal ganglia neuromodulation: Review on basal ganglia deep brain stimulation.

    Science.gov (United States)

    Da Cunha, Claudio; Boschen, Suelen L; Gómez-A, Alexander; Ross, Erika K; Gibson, William S J; Min, Hoon-Ki; Lee, Kendall H; Blaha, Charles D

    2015-11-01

    This review presents state-of-the-art knowledge about the roles of the basal ganglia (BG) in action-selection, cognition, and motivation, and how this knowledge has been used to improve deep brain stimulation (DBS) treatment of neurological and psychiatric disorders. Such pathological conditions include Parkinson's disease, Huntington's disease, Tourette syndrome, depression, and obsessive-compulsive disorder. The first section presents evidence supporting current hypotheses of how the cortico-BG circuitry works to select motor and emotional actions, and how defects in this circuitry can cause symptoms of the BG diseases. Emphasis is given to the role of striatal dopamine on motor performance, motivated behaviors and learning of procedural memories. Next, the use of cutting-edge electrochemical techniques in animal and human studies of BG functioning under normal and disease conditions is discussed. Finally, functional neuroimaging studies are reviewed; these works have shown the relationship between cortico-BG structures activated during DBS and improvement of disease symptoms. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Vasopressin activates Akt/mTOR pathway in smooth muscle cells cultured in high glucose concentration

    Energy Technology Data Exchange (ETDEWEB)

    Montes, Daniela K.; Brenet, Marianne; Muñoz, Vanessa C.; Burgos, Patricia V.; Villanueva, Carolina I. [Department of Physiology, Universidad Austral de Chile, Valdivia 509-9200 (Chile); Figueroa, Carlos D. [Department of Anatomy, Histology and Pathology, Universidad Austral de Chile, Valdivia 509-9200 (Chile); González, Carlos B., E-mail: cbgonzal@uach.cl [Department of Physiology, Universidad Austral de Chile, Valdivia 509-9200 (Chile); Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555 (United States)

    2013-11-29

    Highlights: •AVP induces mTOR phosphorylation in A-10 cells cultured in high glucose concentration. •The mTOR phosphorylation is mediated by the PI3K/Akt pathway activation. •The AVP-induced mTOR phosphorylation inhibited autophagy and stimulated cell proliferation. -- Abstract: Mammalian target of rapamycin (mTOR) complex is a key regulator of autophagy, cell growth and proliferation. Here, we studied the effects of arginine vasopressin (AVP) on mTOR activation in vascular smooth muscle cells cultured in high glucose concentration. AVP induced the mTOR phosphorylation in A-10 cells grown in high glucose, in contrast to cells cultured in normal glucose; wherein, only basal phosphorylation was observed. The AVP-induced mTOR phosphorylation was inhibited by a PI3K inhibitor. Moreover, the AVP-induced mTOR activation inhibited autophagy and increased thymidine incorporation in cells grown in high glucose. This increase was abolished by rapamycin which inhibits the mTORC1 complex formation. Our results suggest that AVP stimulates mTOR phosphorylation by activating the PI3K/Akt signaling pathway and, subsequently, inhibits autophagy and raises cell proliferation in A-10 cells maintained in high glucose concentration.

  1. Basal HIF-1a expression levels are not predictive for radiosensitivity of human cancer cell lines

    International Nuclear Information System (INIS)

    Schilling, D.; Multhoff, G.; Helmholtz Center Munich, CCG - Innate Immunity in Tumor Biology, Munich; Bayer, C.; Emmerich, K.; Molls, M.; Vaupel, P.; Huber, R.M.

    2012-01-01

    High levels of hypoxia inducible factor (HIF)-1a in tumors are reported to be associated with tumor progression and resistance to therapy. To examine the impact of HIF-1a on radioresistance under normoxia, the sensitivity towards irradiation was measured in human tumor cell lines that differ significantly in their basal HIF-1a levels. HIF-1a levels were quantified in lysates of H1339, EPLC-272H, A549, SAS, XF354, FaDu, BHY, and CX- tumor cell lines by ELISA. Protein levels of HIF-1a, HIF-2a, carbonic anhydrase IX (CA IX), and GAPDH were assessed by Western blot analysis. Knock-down experiments were performed using HIF-1a siRNA. Clonogenic survival after irradiation was determined by the colony forming assay. According to their basal HIF-1a status, the tumor cell lines were divided into low (SAS, XF354, FaDu, A549, CX-), intermediate (EPLC-272H, BHY), and high (H1339) HIF-1a expressors. The functionality of the high basal HIF-1a expression in H1339 cells was proven by reduced CA IX expression after knocking-down HIF-1a. Linear regression analysis revealed no correlation between basal HIF-1a levels and the survival fraction at either 2 or 4 Gy in all tumor cell lines investigated. Our data suggest that basal HIF-1a levels in human tumor cell lines do not predict their radiosensitivity under normoxia. (orig.)

  2. Basal cell carcinoma in farmers: an occupation group at high risk.

    Science.gov (United States)

    Szewczyk, Mateusz; Pazdrowski, Jakub; Golusiński, Paweł; Dańczak-Pazdrowska, Aleksandra; Łuczewski, Łukasz; Marszałek, Sławomir; Majchrzak, Ewa; Golusiński, Wojciech

    2016-04-01

    Skin cancer is the most commonly diagnosed cancer type worldwide, and 80 % of skin cancers are basal cell carcinoma (BCC). The main risk factor for developing BCC is exposure to ultraviolet radiation (UVR), particularly high-dose exposure at a young age. Outdoor workers, particularly farmers, are at high risk of developing BCC. However, studies of BCC in this population are scant. To comprehensively evaluate all cases of BCC of the head and neck region treated during the years 2007-2013 at our hospital in Poland, and to compare the tumour characteristics in farmers to non-farmers. Retrospective analysis of 312 patients treated for head and neck BCC during the study period (2007-2013). Most patients (198 cases; 63 %) were males, with 114 females (37 %). Median age was 73 years (range 32-96 years). The most common tumour location was the nose and cheek (114 pts; 37 %) followed by the auricle (82 pts; 26 %), lips (54 pts; 18 %), scalp (26 pts; 8 %), and eye (36 pts; 12 %). The most common disease stage on presentation was stage T2 (104 pts, 33 %), followed by stage T1 (79 pts; 25 %), stage T3 (89 pts; 28 %), and stage T4 (40 pts; 14 %). By occupation, farmers accounted for 33 % of all patients (102 of 312 pts). The most common tumour localisations in the farmer subgroup were the nose and cheek (50 pts; 49 %; p farmer group were significantly younger than non-farmers (62 vs. 73 years; p Farmers were significantly more likely to present disease recurrence (27 vs. 12 % of cases; p farmers. It is therefore necessary to consider enhancing educational programmes and other preventative measures in this occupational group and to evaluate the effectiveness of such programmes.

  3. [Exenteration of the Orbit for Basal Cell Carcinoma].

    Science.gov (United States)

    Furdová, A; Horkovičová, K; Krčová, I; Krásnik, V

    2015-08-01

    Primary treatment of basal cell carcinoma of the lower eyelid and the inner corner is essentially surgical, but advanced lesions require extensive surgical interventions. In some cases it is necessary to continue with the mutilating surgery--exenteration of the orbit. In this work we evaluate the indications of radical solutions in patients with basal cell carcinoma invading the orbit and the subsequent possibility for individually made prosthesis to cover the defect of the cavity. Indications to exenteration of the orbit in patients with basal cell carcinoma findings in 2008-2013. Case report of 2 patients. In period 2008-20013 at the Dept. of Ophthalmology, Comenius University in Bratislava totally 221 patients with histologically confirmed basal cell carcinoma of the eyelids and the inner corner were treated. In 5 cases (2.7 %) with infiltration of the orbit the radical surgical procedure, exenteration was necessary. In 3 patients exenteration was indicated as the first surgical procedure in the treatment of basal cell carcinoma, since they had never visited ophthalmologist before only at in the stage of infiltration of the orbit (stage T4). In one case was indicated exenteration after previous surgical interventions and relapses. After healing the cavity patients got individually prepared epithesis. Surgical treatment of basal cell carcinoma involves the radical removal of the neoplasm entire eyelid and stage T1 or T2 can effectively cure virtually all tumors with satisfactory cosmetic and functional results. In advanced stages (T4 stage) by infiltrating the orbit by basal cell carcinoma exenteration of the orbit is necessary. This surgery is a serious situation for the patient and also for his relatives. Individually made prosthesis helps the patient to be enrolled to the social environment.

  4. Chronic Stress and Adolescents' Mental Health: Modifying Effects of Basal Cortisol and Parental Psychiatric History. The TRAILS Study.

    Science.gov (United States)

    Zandstra, Anna Roos E; Hartman, Catharina A; Nederhof, Esther; van den Heuvel, Edwin R; Dietrich, Andrea; Hoekstra, Pieter J; Ormel, Johan

    2015-08-01

    Large individual differences in adolescent mental health following chronic psychosocial stress suggest moderating factors. We examined two established moderators, basal cortisol and parental psychiatric history, simultaneously. We hypothesized that individuals with high basal cortisol, assumed to indicate high context sensitivity, would show relatively high problem levels following chronic stress, especially in the presence of parental psychiatric history. With Linear Mixed Models, we investigated the hypotheses in 1917 Dutch adolescents (53.2% boys), assessed at ages 11, 13.5, and 16. Low basal cortisol combined with the absence of a parental psychiatric history increased the risk of externalizing but not internalizing problems following chronic stress. Conversely, low basal cortisol combined with a substantial parental psychiatric history increased the risk of internalizing but not externalizing problems following chronic stress. Thus, parental psychiatric history moderated stress- cortisol interactions in predicting psychopathology, but in a different direction than hypothesized. We conclude that the premise that basal cortisol indicates context sensitivity may be too crude. Context sensitivity may not be a general trait but may depend on the nature of the context (e.g., type or duration of stress exposure) and on the outcome of interest (e.g., internalizing vs. externalizing problems). Although consistent across informants, our findings need replication.

  5. Calmodulin-activated cyclic nucleotide phosphodiesterase from brain. Relationship of subunit structure to activity assessed by radiation inactivation

    International Nuclear Information System (INIS)

    Kincaid, R.L.; Kemdner, E.; Manganiello, V.C.; Osborne, J.C.; Vaughan, M.

    1981-01-01

    The apparent target sizes of the basal and calmodulin-dependent activities of calmodulin-activated phosphodiesterase from bovine brain were estimated using target theory analysis of data from radiation inactivation experiments. Whether crude or highly purified samples were irradiated, the following results were obtained. Low doses of radiation caused a 10 to 15% increase in basal activity, which, with further irradiation, decayed with an apparent target size of approx.60,000 daltons. Calmodulin-dependent activity decayed with an apparent target size of approx.105,000 daltons. The percentage stimulation of enzyme activity by calmodulin decreased markedly as a function of radiation dosage. These observations are consistent with results predicted by computer-assisted modeling based on the assumptions that: 1) the calmodulin-activated phosphodiesterase exists as a mixture of monomers which are fully active in the absence of calmodulin and dimers which are inactive in the absence of calmodulin; 2) in the presence of calmodulin, a dimer exhibits activity equal to that of two monomers; 3) on radiation destruction of a dimer, an active monomer is generated. This monomer-dimer hypothesis provides a plausible explanation for and definition of basal and calmodulin-dependent phosphodiesterase activity

  6. Traumatic bilateral basal ganglia hematoma: A report of two cases

    OpenAIRE

    Bhargava, Pranshu; Grewal, Sarvpreet Singh; Gupta, Bharat; Jain, Vikas; Sobti, Harman

    2012-01-01

    Traumatic Basal ganglia hemorrhage is relatively uncommon. Bilateral basal ganglia hematoma after trauma is extremely rare and is limited to case reports. We report two cases of traumatic bilateral basal ganglia hemorrhage, and review the literature in brief. Both cases were managed conservatively.

  7. PreSMA stimulation changes task-free functional connectivity in the fronto-basal-ganglia that correlates with response inhibition efficiency.

    Science.gov (United States)

    Xu, Benjamin; Sandrini, Marco; Wang, Wen-Tung; Smith, Jason F; Sarlls, Joelle E; Awosika, Oluwole; Butman, John A; Horwitz, Barry; Cohen, Leonardo G

    2016-09-01

    Previous work using transcranial magnetic stimulation (TMS) demonstrated that the right presupplementary motor area (preSMA), a node in the fronto-basal-ganglia network, is critical for response inhibition. However, TMS influences interconnected regions, raising the possibility of a link between the preSMA activity and the functional connectivity within the network. To understand this relationship, we applied single-pulse TMS to the right preSMA during functional magnetic resonance imaging when the subjects were at rest to examine changes in neural activity and functional connectivity within the network in relation to the efficiency of response inhibition evaluated with a stop-signal task. The results showed that preSMA-TMS increased activation in the right inferior-frontal cortex (rIFC) and basal ganglia and modulated their task-free functional connectivity. Both the TMS-induced changes in the basal-ganglia activation and the functional connectivity between rIFC and left striatum, and of the overall network correlated with the efficiency of response inhibition and with the white-matter microstructure along the preSMA-rIFC pathway. These results suggest that the task-free functional and structural connectivity between the rIFCop and basal ganglia are critical to the efficiency of response inhibition. Hum Brain Mapp 37:3236-3249, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  8. Improvement of basal conditions knowledge in Antarctica using data assimilation methods

    Science.gov (United States)

    Mosbeux, C.; Gillet-Chaulet, F.; Gagliardini, O.

    2017-12-01

    The current global warming seems to have direct consequences on ice-sheet mass loss. Unfortunately, as highlighted in the last IPCC report, current ice-sheets models face several difficulties in assessing the future evolution of the dynamics of ice sheets for the next century. Indeed, projections are still plagued with high uncertainties partially due to the poor representation of occurring physical processes, but also due to the poor initialisation of ice flow models. More specifically, simulations are very sensitive to initial parameters such as the basal friction between ice-sheet and bedrock and the bedrock topography which are still badly known because of a lack of direct observations or large uncertainty on measurements. Improving the knowledge of these two parameters in Greenland and Antarctica is therefore a prerequisite for making reliable projections. Data assimilation methods have been developed in order to overcome this problem such as the Bayesian approach of Pralong and Gudmundsson (2009) or the adjoint method tested by Goldberg and Heimbach (2013) and Perego et al. (2014). The present work is based on two different assimilation algorithms to better constrain both basal drag and bedrock elevation parameters. The first algorithm is entirely based on the adjoint method while the second one uses an iterative method coupling inversion of basal friction based on an adjoint method and through an inversion of bedrock topography using a nudging method. Both algorithms have been implemented in the finite element ice sheet and ice flow model Elmer/Ice and have been tested in a twin experiment showing a clear improvement of both parameters knowledge (Mosbeux et al., 2016). Here, the methods are applied to a real 3D case in East Antarctica and with an ensemble method approach. The application of both algorithms reduces the uncertainty on basal conditions, for instance by providing more details to the basal geometry when compared to usual DEM. Moreover, as in the

  9. Dysfunctions of the basal ganglia-cerebellar-thalamo-cortical system produce motor tics in Tourette syndrome.

    Science.gov (United States)

    Caligiore, Daniele; Mannella, Francesco; Arbib, Michael A; Baldassarre, Gianluca

    2017-03-01

    Motor tics are a cardinal feature of Tourette syndrome and are traditionally associated with an excess of striatal dopamine in the basal ganglia. Recent evidence increasingly supports a more articulated view where cerebellum and cortex, working closely in concert with basal ganglia, are also involved in tic production. Building on such evidence, this article proposes a computational model of the basal ganglia-cerebellar-thalamo-cortical system to study how motor tics are generated in Tourette syndrome. In particular, the model: (i) reproduces the main results of recent experiments about the involvement of the basal ganglia-cerebellar-thalamo-cortical system in tic generation; (ii) suggests an explanation of the system-level mechanisms underlying motor tic production: in this respect, the model predicts that the interplay between dopaminergic signal and cortical activity contributes to triggering the tic event and that the recently discovered basal ganglia-cerebellar anatomical pathway may support the involvement of the cerebellum in tic production; (iii) furnishes predictions on the amount of tics generated when striatal dopamine increases and when the cortex is externally stimulated. These predictions could be important in identifying new brain target areas for future therapies. Finally, the model represents the first computational attempt to study the role of the recently discovered basal ganglia-cerebellar anatomical links. Studying this non-cortex-mediated basal ganglia-cerebellar interaction could radically change our perspective about how these areas interact with each other and with the cortex. Overall, the model also shows the utility of casting Tourette syndrome within a system-level perspective rather than viewing it as related to the dysfunction of a single brain area.

  10. Dysfunctions of the basal ganglia-cerebellar-thalamo-cortical system produce motor tics in Tourette syndrome.

    Directory of Open Access Journals (Sweden)

    Daniele Caligiore

    2017-03-01

    Full Text Available Motor tics are a cardinal feature of Tourette syndrome and are traditionally associated with an excess of striatal dopamine in the basal ganglia. Recent evidence increasingly supports a more articulated view where cerebellum and cortex, working closely in concert with basal ganglia, are also involved in tic production. Building on such evidence, this article proposes a computational model of the basal ganglia-cerebellar-thalamo-cortical system to study how motor tics are generated in Tourette syndrome. In particular, the model: (i reproduces the main results of recent experiments about the involvement of the basal ganglia-cerebellar-thalamo-cortical system in tic generation; (ii suggests an explanation of the system-level mechanisms underlying motor tic production: in this respect, the model predicts that the interplay between dopaminergic signal and cortical activity contributes to triggering the tic event and that the recently discovered basal ganglia-cerebellar anatomical pathway may support the involvement of the cerebellum in tic production; (iii furnishes predictions on the amount of tics generated when striatal dopamine increases and when the cortex is externally stimulated. These predictions could be important in identifying new brain target areas for future therapies. Finally, the model represents the first computational attempt to study the role of the recently discovered basal ganglia-cerebellar anatomical links. Studying this non-cortex-mediated basal ganglia-cerebellar interaction could radically change our perspective about how these areas interact with each other and with the cortex. Overall, the model also shows the utility of casting Tourette syndrome within a system-level perspective rather than viewing it as related to the dysfunction of a single brain area.

  11. Basal ganglia impairments in autism spectrum disorder are related to abnormal signal gating to prefrontal cortex.

    Science.gov (United States)

    Prat, Chantel S; Stocco, Andrea; Neuhaus, Emily; Kleinhans, Natalia M

    2016-10-01

    Research on the biological basis of autism spectrum disorder has yielded a list of brain abnormalities that are arguably as diverse as the set of behavioral symptoms that characterize the disorder. Among these are patterns of abnormal cortical connectivity and abnormal basal ganglia development. In attempts to integrate the existing literature, the current paper tests the hypothesis that impairments in the basal ganglia's function to flexibly select and route task-relevant neural signals to the prefrontal cortex underpins patterns of abnormal synchronization between the prefrontal cortex and other cortical processing centers observed in individuals with autism spectrum disorder (ASD). We tested this hypothesis using a Dynamic Causal Modeling analysis of neuroimaging data collected from 16 individuals with ASD (mean age=25.3 years; 6 female) and 17 age- and IQ-matched neurotypical controls (mean age=25.6, 6 female), who performed a Go/No-Go test of executive functioning. Consistent with the hypothesis tested, a random-effects Bayesian model selection procedure determined that a model of network connectivity in which basal ganglia activation modulated connectivity between the prefrontal cortex and other key cortical processing centers best fit the data of both neurotypicals and individuals with ASD. Follow-up analyses suggested that the largest group differences were observed for modulation of connectivity between prefrontal cortex and the sensory input region in the occipital lobe [t(31)=2.03, p=0.025]. Specifically, basal ganglia activation was associated with a small decrease in synchronization between the occipital region and prefrontal cortical regions in controls; however, in individuals with ASD, basal ganglia activation resulted in increased synchronization between the occipital region and the prefrontal cortex. We propose that this increased synchronization may reflect a failure in basal ganglia signal gating mechanisms, resulting in a non-selective copying

  12. Immunohistochemical Characteristics of Triple Negative/Basal-like Breast Cancer

    OpenAIRE

    Emel Ebru PALA; Ümit BAYOL; Süheyla CUMURCU; Elif KESKİN

    2012-01-01

    Objective: Triple-negative-breast-cancer that accounts for 10-20% of all breast carcinomas is defined by the lack of estrogen receptor, progesterone receptor, HER2 expression, and agressive clinical behavior. Triple-negative-breast-cancer is categorized into basal like and other types. The basal-like subtype is characterized by the expression of myoepithelial/basal markers.Material and Method: We studied 41 immunohistochemically triplenegative- breast-cancer patients to determine EGFR, Cytoke...

  13. Basal-plane stacking faults in non-polar GaN studied by off-axis electron holography

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Lewis Z-Y; Rao, D V Sridhara; Kappers, M J; Humphreys, C J [Department of Materials Science and Metallurgy, University of Cambridge, Pembroke Street, Cambridge, CB2 3QZ (United Kingdom); Geiger, D, E-mail: ZL249@cam.ac.u [Triebenberg Laboratory, Institute for Structure Physics, Technische Universitaet Dresden, D-01062 Dresden (Germany)

    2010-02-01

    We have studied basal-plane stacking faults in a non-polar (11-20) GaN epilayer using high-resolution electron microscopy and off-axis electron holography. The microstructure of the basal-plane stacking faults (BSFs) has been determined to be I{sub 1} type from high-resolution TEM images. High-resolution holograms along the [11-20] zone axis were obtained by off-axis electron holography on a Cs-corrected TEM, providing {approx}2 A spatial resolution in the reconstructed amplitude and phase images. Phase fluctuations across the stacking faults were detected, suggesting the presence of a built-in electric field. The uncertainties in the experiments and their interpretation are discussed.

  14. Partial denervation of sub-basal axons persists following debridement wounds to the mouse cornea.

    Science.gov (United States)

    Pajoohesh-Ganji, Ahdeah; Pal-Ghosh, Sonali; Tadvalkar, Gauri; Kyne, Briana M; Saban, Daniel R; Stepp, Mary Ann

    2015-11-01

    Although sensory reinnervation occurs after injury in the peripheral nervous system, poor reinnervation in the elderly and those with diabetes often leads to pathology. Here we quantify sub-basal axon density in the central and peripheral mouse cornea over time after three different types of injury. The mouse cornea is highly innervated with a dense array of sub-basal nerves that form a spiral called the vortex at the corneal center or apex; these nerves are readily detected within flat mounted corneas. After anesthesia, corneal epithelial cells were removed using either a dulled blade or a rotating burr within an area demarcated centrally with a 1.5 mm trephine. A third wound type, superficial trephination, involved demarcating the area with the 1.5 mm trephine but not removing cells. By 7 days after superficial trephination, sub-basal axon density returns to control levels; by 28 days the vortex reforms. Although axon density is similar to control 14 days after dulled blade and rotating burr wounding, defects in axon morphology at the corneal apex remain. After 14 days, axons retract from the center leaving the sub-basal axon density reduced by 37.2 and 36.8% at 28 days after dulled blade and rotating burr wounding, respectively, compared with control. Assessment of inflammation using flow cytometry shows that persistent inflammation is not a factor in the incomplete reinnervation. Expression of mRNAs encoding 22 regeneration-associated genes involved in axon targeting assessed by QPCR reveals that netrin-1 and ephrin signaling are altered after wounding. Subpopulations of corneal epithelial basal cells at the corneal apex stop expressing ki67 as early as 7 days after injury and by 14 and 28 days after wounding, many of these basal cells undergo apoptosis and die. Although sub-basal axons are restored to their normal density and morphology after superficial trephination, sub-basal axon recovery is partial after debridement wounds. The increase in corneal

  15. Basal ganglia dysfunction in idiopathic REM sleep behaviour disorder parallels that in early Parkinson's disease.

    Science.gov (United States)

    Rolinski, Michal; Griffanti, Ludovica; Piccini, Paola; Roussakis, Andreas A; Szewczyk-Krolikowski, Konrad; Menke, Ricarda A; Quinnell, Timothy; Zaiwalla, Zenobia; Klein, Johannes C; Mackay, Clare E; Hu, Michele T M

    2016-08-01

    SEE POSTUMA DOI101093/AWW131 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Resting state functional magnetic resonance imaging dysfunction within the basal ganglia network is a feature of early Parkinson's disease and may be a diagnostic biomarker of basal ganglia dysfunction. Currently, it is unclear whether these changes are present in so-called idiopathic rapid eye movement sleep behaviour disorder, a condition associated with a high rate of future conversion to Parkinson's disease. In this study, we explore the utility of resting state functional magnetic resonance imaging to detect basal ganglia network dysfunction in rapid eye movement sleep behaviour disorder. We compare these data to a set of healthy control subjects, and to a set of patients with established early Parkinson's disease. Furthermore, we explore the relationship between resting state functional magnetic resonance imaging basal ganglia network dysfunction and loss of dopaminergic neurons assessed with dopamine transporter single photon emission computerized tomography, and perform morphometric analyses to assess grey matter loss. Twenty-six patients with polysomnographically-established rapid eye movement sleep behaviour disorder, 48 patients with Parkinson's disease and 23 healthy control subjects were included in this study. Resting state networks were isolated from task-free functional magnetic resonance imaging data using dual regression with a template derived from a separate cohort of 80 elderly healthy control participants. Resting state functional magnetic resonance imaging parameter estimates were extracted from the study subjects in the basal ganglia network. In addition, eight patients with rapid eye movement sleep behaviour disorder, 10 with Parkinson's disease and 10 control subjects received (123)I-ioflupane single photon emission computerized tomography. We tested for reduction of basal ganglia network connectivity, and for loss of tracer uptake in rapid eye movement sleep

  16. CT and MRI diagnosis of traumatic basal ganglia hemorrhage

    International Nuclear Information System (INIS)

    Wu Shike; Zhang Yalin; Xu Derong; Zou Gaowei; Chen Dan; He Sujun; Zhou Lichao

    2009-01-01

    Objective: To analyze CT and MRI features of traumatic basal ganglia hemorrhage and investigate the diagnostic value. Methods: 21 cases with traumatic basal ganglia hemorrhage diagnosed by clinic, CT and MRI in our hospital were collected in this study Plain CT scan were immediately performed in 21 cases after injury, plain MR scan were performed in 1 to 3 days. 12 cases of them underwent diffusion weighted imagine (DWI). The CT and MRI findings were retrospectively summarized. Results: 8 cases were found with simple traumatic basal ganglia hemorrhage. Complexity of basal ganglia hemorrhage occurred in 13 cases, 6 cases combined with subdural hemorrhage, 3 cases with epidural hematoma, 2 cases with subarachnoid hemorrhage, 6 cases with brain contusion and laceration in other locations, 4 cases with skull fracture. 26 lesions of basal ganglia hematoma were showed in 21 cases, 14 lesions of pallidum hemorrhage in 11 cases confirmed by MR could not be distinguished from calcification at the fast CT scan. 5 more lesions of brain contusion and laceration and 4 more lesions of brain white matter laceration were found by MR. Conclusion: CT in combination with MRI can diagnose traumatic basal ganglia hemorrhage and its complications early, comprehensively and accurately, which plays an important role in the clinical therapy selection and prognosis evaluation. (authors)

  17. Clinicopathological evaluation of radiation induced basal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Meibodi Naser

    2008-01-01

    Full Text Available Background: Development of skin neoplasms is one of the most important chronic complications of radiation therapy. Basal cell carcinoma (BCC is the most frequent carcinoma occurring at the region of the body to which radiotherapy was delivered. Aim: The aim of this study was to evaluate clinical and histological aspects of basal cell carcinoma in patients with a history of radiotherapy. Materials and Methods: Medical records and microscopic slides of 80 patients with basal cell carcinoma who had received radiotherapy (1996-2006 were reviewed in pathology department of Imam Reza hospital of Mashhad, Iran. Collected data were analyzed statistically using descriptive test. Results: 60 men and 20 women were included, majority of them in their sixties. Plaque was the most common clinical pattern of basal cell carcinoma. Fifty one percent of the patients had pigmented and 42.5% had multiple lesions. Scalp was the most common site of involvement. Histologically, macronodular and pigmented carcinoma were the most predominant forms of basal cell carcinoma. Discussion: Majority of patients had scalp involvement and multiple lesions. Nodular and pigmented forms were the most common histological findings. We suggest the need for close supervision in patients with a history of radio therapy in the past.

  18. Basal cerebral glucose distribution in long-term post-traumatic stress disorder.

    Science.gov (United States)

    Molina, Mario Enrique; Isoardi, Roberto; Prado, Marcela Nathalie; Bentolila, Silvia

    2010-03-01

    The purpose of this investigation was to study basal cerebral glucose absorption patterns associated to long-term post-traumatic stress disorder. Fluorodeoxyglucose positron emission tomography (FDG-PET) and statistic parametric mapping (SPM) were used to compare regional cerebral glucose absorption between 15 war veterans (Hispanic men, aged 39-41 (M = 39.5, SD = 0.84)) diagnosed with post-traumatic stress disorder (PTSD) based on DSM-IV criteria, and a matching control group of six asymptomatic veterans. This study was conducted 20 years after the traumatic events. PTSD patients presented relatively diminished activity (P<0.005) in: cingulate gyri, precuneus, insula, hippocampus; frontal, pre-frontal and post-central regions; lingual, calcarine, occipital medial and superior gyri, and verbal and paraverbal areas. Relativeley augmented activity (P<0.005) was observed in PTSD patients in: fusiform, temporal superior, medial, and inferior gyri; occipital medial, inferior and lingual gyri; precuneus, and cerebellum. The amygdala and the thalamus showed normal metabolic activity. Various brain regions that showed diminished activity (limbic, frontal and prefrontal cortex, multimodal parieto-occipital areas and verbal and paraverbal areas) have evolved lately, and sub-serve highly complex cognitive and behavioural functions. Metabolic activity patterns are comparable to those observed in personality disorders of the borderline type.

  19. Basal Cell Carcinoma in Gorlin's Patients: a Matter of Fibroblasts-Led Protumoral Microenvironment?

    Science.gov (United States)

    Gache, Yannick; Brellier, Florence; Rouanet, Sophie; Al-Qaraghuli, Sahar; Goncalves-Maia, Maria; Burty-Valin, Elodie; Barnay, Stéphanie; Scarzello, Sabine; Ruat, Martial; Sevenet, Nicolas; Avril, Marie-Françoise; Magnaldo, Thierry

    2015-01-01

    Basal cell carcinoma (BCC) is the commonest tumor in human. About 70% sporadic BCCs bear somatic mutations in the PATCHED1 tumor suppressor gene which encodes the receptor for the Sonic Hedgehog morphogen (SHH). PATCHED1 germinal mutations are associated with the dominant Nevoid Basal Cell Carcinoma Syndrome (NBCCS), a major hallmark of which is a high susceptibility to BCCs. Although the vast majority of sporadic BCCs arises exclusively in sun exposed skin areas, 40 to 50% BCCs from NBCCS patients develop in non photo-exposed skin. Since overwhelming evidences indicate that microenvironment may both be modified by- and influence the- epithelial tumor, we hypothesized that NBCCS fibroblasts could contribute to BCCs in NBCCS patients, notably those developing in non photo-exposed skin areas. The functional impact of NBCCS fibroblasts was then assessed in organotypic skin cultures with control keratinocytes. Onset of epidermal differentiation was delayed in the presence of primary NBCCS fibroblasts. Unexpectedly, keratinocyte proliferation was severely reduced and showed high levels of nuclear P53 in both organotypic skin cultures and in fibroblast-led conditioning experiments. However, in spite of increased levels of senescence associated β-galactosidase activity in keratinocytes cultured in the presence of medium conditioned by NBCCS fibroblasts, we failed to observe activation of P16 and P21 and then of bona fide features of senescence. Constitutive extinction of P53 in WT keratinocytes resulted in an invasive phenotype in the presence of NBCCS fibroblasts. Finally, we found that expression of SHH was limited to fibroblasts but was dependent on the presence of keratinocytes. Inhibition of SHH binding resulted in improved epidermal morphogenesis. Altogether, these data suggest that the repertoire of diffusible factors (including SHH) expressed by primary NBCCS fibroblasts generate a stress affecting keratinocytes behavior and epidermal homeostasis. Our findings

  20. Serum Fetuin-A Levels in Patients with Bilateral Basal Ganglia Calcification.

    Science.gov (United States)

    Demiryurek, Bekir Enes; Gundogdu, Asli Aksoy

    2018-02-14

    The idiopathic basal ganglia calcification (Fahr syndrome) may occur due to senility. Fetuin-A is a negative acute phase reactant which inhibits calcium-phosphorus precipitation and vascular calcification. In this study, we aimed to evaluate whether serum fetuin-A levels correlate with bilateral basal ganglia calcification. Forty-five patients who had bilateral basal ganglia calcification on brain CT were selected according to the inclusion and exclusion criteria, and 45 age and gender-matched subjects without basal ganglia calcification were included for the control group. Serum fetuin-A levels were measured from venous blood samples. All participants were divided into two groups; with and without basal ganglia calcification. These groups were divided into subgroups regarding age (18-32 and 33-45 years of age) and gender (male, female). We detected lower levels of serum fetuin-A in patients with basal ganglia calcification compared with the subjects without basal ganglia calcification. In all subgroups (female, male, 18-32 years and 33-45 years), mean fetuin-A levels were significantly lower in patients with basal ganglia calcification (p = 0.017, p = 0.014, p = 0.024, p = 0.026, p = 0.01 respectively). And statistically significantly lower levels of fetuin-A was found to be correlated with the increasing densities of calcification in the calcified basal ganglia group (p-value: <0.001). Considering the role of fetuin-A in tissue calcification and inflammation, higher serum fetuin-A levels should be measured in patients with basal ganglia calcification. We believe that the measurement of serum fetuin-A may play a role in the prediction of basal ganglia calcification as a biomarker. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. The wide-spread presence of rib-like patterns in basal shear of ice streams detected by surface data inversion

    Science.gov (United States)

    Sergienko, O. V.

    2013-12-01

    The direct observations of the basal conditions under continental-scale ice sheets are logistically impossible. A possible approach to estimate conditions at the ice - bed interface is from surface observations by means of inverse methods. The recent advances in remote and ground-based observations have allowed to acquire a wealth observations from Greenland and Antarctic ice sheets. Using high-resolution data sets of ice surface and bed elevations and surface velocities, inversions for basal conditions have been performed for several ice streams in Greenland and Antarctica. The inversion results reveal the wide-spread presence of rib-like spatial structures in basal shear. The analysis of the hydraulic potential distribution shows that these rib-like structures co-locate with highs of the gradient of hydraulic potential. This suggests that subglacial water plays a role in the development and evolution of the basal shear ribs.

  2. Activation of molybdenite concentrate of KM-4 index mark

    International Nuclear Information System (INIS)

    Bogomolov, A.M.; Mitskevich, A.A.; Shuvaev, A.P.

    1991-01-01

    A study was made on the effect of mechanical activation in DU-73 disintegrator on structural characteristics, dissolution rate and leaching degree of molybdenite in KM-4 concentrated. The following facts were established in experiments: high amorphization degree of basal planes (plate surfaces) ∼ 80%, increase of oxidation degree by 35% on the average. All this testify to the fact, that oxidation reaction in activated molybdenite proceeds both on plate edges and on broken basal planes

  3. Amyloid in basal cell carcinoma and seborrheic keratosis

    DEFF Research Database (Denmark)

    Olsen, K E; Westermark, Per

    1994-01-01

    The frequency of amyloid substance was studied in two different types of skin tumours: basal cell carcinoma and seborrheic keratosis. In 9 out of 49 cases of seborrheic keratosis amyloid substance was found. In the basal cell carcinomas, 194 out of 260 cases showed amyloid deposits, a rate...

  4. The influence of basal-ice debris on patterns and rates of glacial erosion

    Science.gov (United States)

    Ugelvig, Sofie V.; Egholm, David L.

    2018-05-01

    Glaciers have played a key role for shaping much of Earth's high topography during the cold periods of the Late Cenozoic. However, despite of their distinct influence on landscapes, the mechanisms of glacial erosion, and the properties that determine their rate of operation, are still poorly understood. Theoretical models of subglacial erosion generally highlight the influence of basal sliding in setting the pace of erosion, but they also point to a strong influence of other subglacial properties, such as effective bed pressure and basal-ice debris concentration. The latter properties are, however, not easily measured in existing glaciers, and hence their influence cannot readily be confirmed by observations. In order to better connect theoretical models for erosion to measurable properties in glaciers, we used computational landscape evolution experiments to study the expected influence of basal-ice debris concentration for subglacial abrasion at the scale of glaciers. The computational experiments couple the two erosion processes of quarrying and abrasion, and furthermore integrate the flow of ice and transport of debris within the ice, thus allowing for the study of dynamic feedbacks between subglacial erosion and systematic glacier-scale variations in basal-ice debris concentration. The experiments explored several physics-based models for glacial erosion, in combination with different models for basal sliding to elucidate the relationship between sliding speed, erosion rate and basal-ice debris concentration. The results demonstrate how differences in debris concentration can explain large variations in measured rates. The experiments also provide a simple explanation for the observed dependence of glacier-averaged rate of erosion on glacier size: that large glacier uplands feed more debris into their lower-elevation parts, thereby strengthening their erosive power.

  5. Effective deep brain stimulation suppresses low frequency network oscillations in the basal ganglia by regularizing neural firing patterns

    Science.gov (United States)

    McConnell, George C.; So, Rosa Q.; Hilliard, Justin D; Lopomo, Paola; Grill, Warren M.

    2012-01-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for the motor symptoms of Parkinson’s disease (PD). The effects of DBS depend strongly on stimulation frequency: high frequencies (>90Hz) improve motor symptoms, while low frequencies (basal ganglia were studied in the unilateral 6-hydroxydopamine lesioned rat model of PD. Only high frequency DBS reversed motor symptoms and the effectiveness of DBS depended strongly on stimulation frequency in a manner reminiscent of its clinical effects in persons with PD. Quantification of single-unit activity in the globus pallidus externa (GPe) and substantia nigra reticulata (SNr) revealed that high frequency DBS, but not low frequency DBS, reduced pathological low frequency oscillations (~9Hz) and entrained neurons to fire at the stimulation frequency. Similarly, the coherence between simultaneously recorded pairs of neurons within and across GPe and SNr shifted from the pathological low frequency band to the stimulation frequency during high frequency DBS, but not during low frequency DBS. The changes in firing patterns in basal ganglia neurons were not correlated with changes in firing rate. These results indicate that high frequency DBS is more effective than low frequency DBS, not as a result of changes in firing rate, but rather due to its ability to replace pathological low frequency network oscillations with a regularized pattern of neuronal firing. PMID:23136407

  6. Effective deep brain stimulation suppresses low-frequency network oscillations in the basal ganglia by regularizing neural firing patterns.

    Science.gov (United States)

    McConnell, George C; So, Rosa Q; Hilliard, Justin D; Lopomo, Paola; Grill, Warren M

    2012-11-07

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for the motor symptoms of Parkinson's disease (PD). The effects of DBS depend strongly on stimulation frequency: high frequencies (>90 Hz) improve motor symptoms, while low frequencies (basal ganglia were studied in the unilateral 6-hydroxydopamine lesioned rat model of PD. Only high-frequency DBS reversed motor symptoms, and the effectiveness of DBS depended strongly on stimulation frequency in a manner reminiscent of its clinical effects in persons with PD. Quantification of single-unit activity in the globus pallidus externa (GPe) and substantia nigra reticulata (SNr) revealed that high-frequency DBS, but not low-frequency DBS, reduced pathological low-frequency oscillations (∼9 Hz) and entrained neurons to fire at the stimulation frequency. Similarly, the coherence between simultaneously recorded pairs of neurons within and across GPe and SNr shifted from the pathological low-frequency band to the stimulation frequency during high-frequency DBS, but not during low-frequency DBS. The changes in firing patterns in basal ganglia neurons were not correlated with changes in firing rate. These results indicate that high-frequency DBS is more effective than low-frequency DBS, not as a result of changes in firing rate, but rather due to its ability to replace pathological low-frequency network oscillations with a regularized pattern of neuronal firing.

  7. The terminal basal mitosis of chicken retinal Lim1 horizontal cells is not sensitive to cisplatin-induced cell cycle arrest.

    Science.gov (United States)

    Shirazi Fard, Shahrzad; Thyselius, Malin; All-Ericsson, Charlotta; Hallböök, Finn

    2014-01-01

    For proper development, cells need to coordinate proliferation and cell cycle-exit. This is mediated by a cascade of proteins making sure that each phase of the cell cycle is controlled before the initiation of the next. Retinal progenitor cells divide during the process of interkinetic nuclear migration, where they undergo S-phase on the basal side, followed by mitoses on the apical side of the neuroepithelium. The final cell cycle of chicken retinal horizontal cells (HCs) is an exception to this general cell cycle behavior. Lim1 expressing (+) horizontal progenitor cells (HPCs) have a heterogenic final cell cycle, with some cells undergoing a terminal mitosis on the basal side of the retina. The results in this study show that this terminal basal mitosis of Lim1+ HPCs is not dependent on Chk1/2 for its regulation compared to retinal cells undergoing interkinetic nuclear migration. Neither activating nor blocking Chk1 had an effect on the basal mitosis of Lim1+ HPCs. Furthermore, the Lim1+ HPCs were not sensitive to cisplatin-induced DNA damage and were able to continue into mitosis in the presence of γ-H2AX without activation of caspase-3. However, Nutlin3a-induced expression of p21 did reduce the mitoses, suggesting the presence of a functional p53/p21 response in HPCs. In contrast, the apical mitoses were blocked upon activation of either Chk1/2 or p21, indicating the importance of these proteins during the process of interkinetic nuclear migration. Inhibiting Cdk1 blocked M-phase transition both for apical and basal mitoses. This confirmed that the cyclin B1-Cdk1 complex was active and functional during the basal mitosis of Lim1+ HPCs. The regulation of the final cell cycle of Lim1+ HPCs is of particular interest since it has been shown that the HCs are able to sustain persistent DNA damage, remain in the cell cycle for an extended period of time and, consequently, survive for months.

  8. computed tomography features of basal ganglia and periventricular

    African Journals Online (AJOL)

    HIV is probably the most common cause of basal ganglia and periventricular calcification today. on-enhanced computed tomography (NECT) shows diffuse cerebral atrophy in 90% of cases. Bilateral, symmetrical basal ganglia calcification is seen in 30% of cases, but virtually never before 1 year of age.1. CMV (FIG.2).

  9. Effects of Basal Defoliation on Wine Aromas: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Yu Wang

    2018-03-01

    Full Text Available Basal defoliation, as one of the most common viticulture management practices to modify fruit zone microclimates, has been widely applied aiming at improving wine quality. Wine aroma contributes greatly to wine quality, yet the effects of basal defoliation on wine aromas show discrepancies according to previous studies. This study is a meta-analysis performed to dissect the factors related to the influence of basal defoliation on volatile compounds in wine. Timing of basal defoliation plays an important role in the concentration of varietal aromas in wine. Pre-veraison defoliation induces an increase in β-damascenone and linalool as well as a reduction in 3-isobutyl-2-methoxypyrazine (IBMP. The effects of basal defoliation on certain volatile compounds relative to fermentation aromas in wine (1-hexanol, β-phenylethanol, 2-phenylethyl acetate, decanoic acid, and ethyl octanoate depend on grape maturity. There are also other factors, such as cultivar and climate conditions, that might be responsible for the effect of basal defoliation on wine aromas. The concentrations of isobutanol, isoamyl alcohol, hexanoic acid, and octanoic acid as well as ethyl isobutyrate, ethyl hexanoate, ethyl isovalerate, and ethyl decanoate in wine are not markedly affected by basal defoliation. Due to limited studies included in this meta-analysis, more trials are needed to confirm the current findings.

  10. Giant basal cell carcinoma Carcinoma basocelular gigante

    Directory of Open Access Journals (Sweden)

    Nilton Nasser

    2012-06-01

    Full Text Available The basal cell carcinoma is the most common skin cancer but the giant vegetating basal cell carcinoma reaches less than 0.5 % of all basal cell carcinoma types. The Giant BCC, defined as a lesion with more than 5 cm at its largest diameter, is a rare form of BCC and commonly occurs on the trunk. This patient, male, 42 years old presents a Giant Basal Cell Carcinoma which reaches 180 cm2 on the right shoulder and was negligent in looking for treatment. Surgical treatment was performed and no signs of dissemination or local recurrence have been detected after follow up of five years.O carcinoma basocelular é o tipo mais comum de câncer de pele, mas o carcinoma basocelular gigante vegetante não atinge 0,5% de todos os tipos de carcinomas basocelulares. O Carcinoma Basocelular Gigante, definido como lesão maior que 5 cm no maior diâmetro, é uma forma rara de carcinoma basocelular e comumente ocorre no tronco. Este paciente apresenta um Carcinoma Basocelular Gigante com 180cm² no ombro direito e foi negligente em procurar tratamento. Foi realizado tratamento cirúrgico e nenhum sinal de disseminação ou recorrência local foi detectada após 5 anos.

  11. Regulation of basal and reserve cardiac pacemaker function by interactions of cAMP mediated PKA-dependent Ca2+ cycling with surface membrane channels

    Science.gov (United States)

    Vinogradova, Tatiana M.; Lakatta, Edward G.

    2009-01-01

    Decades of intensive research of primary cardiac pacemaker, the sinoatrial node, have established potential roles of specific membrane channels in the generation of the diastolic depolarization, the major mechanism allowing sinoatrial node cells generate spontaneous beating. During the last three decades, multiple studies made either in the isolated sinoatrial node or sinoatrial node cells have demonstrated a pivotal role of Ca2+ and, specifically Ca2+-release from sarcoplasmic reticulum, for spontaneous beating of cardiac pacemaker. Recently, spontaneous, rhythmic local subsarcolemmal Ca2+ releases from ryanodine receptors during late half of the diastolic depolarization have been implicated as a vital factor in the generation of sinoatrial node cells spontaneous firing. Local Ca2+ releases are driven by a unique combination of high basal cAMP production by adenylyl cyclases, high basal cAMP degradation by phosphodiesterases and a high level of cAMP-mediated PKA-dependent phosphorylation. These local Ca2+ releases activate an inward Na+-Ca2+ exchange current which accelerates the terminal diastolic depolarization rate and, thus, controls the spontaneous pacemaker firing. Both the basal primary pacemaker beating rate and its modulation via β-adrenergic receptor stimulation appear to be critically dependent upon intact RyR function and local subsarcolemmal sarcoplasmic reticulum generated Ca2+ releases. This review aspires to integrate the traditional viewpoint that has emphasized the supremacy of the ensemble of surface membrane ion channels in spontaneous firing of the primary cardiac pacemaker, and these novel perspectives of cAMP-mediated PKA-dependent Ca2+ cycling in regulation of the heart pacemaker clock, both in the basal state and during β-adrenergic receptor stimulation. PMID:19573534

  12. Tissue microarrays for testing basal biomarkers in familial breast cancer cases

    Directory of Open Access Journals (Sweden)

    Rozany Mucha Dufloth

    Full Text Available CONTEXT AND OBJECTIVE: The proteins p63, p-cadherin and CK5 are consistently expressed by the basal and myoepithelial cells of the breast, although their expression in sporadic and familial breast cancer cases has yet to be fully defined. The aim here was to study the basal immunopro-file of a breast cancer case series using tissue microarray technology. DESIGN AND SETTING: This was a cross-sectional study at Universidade Estadual de Campinas, Brazil, and the Institute of Pathology and Mo-lecular Immunology, Porto, Portugal. METHODS: Immunohistochemistry using the antibodies p63, CK5 and p-cadherin, and also estrogen receptor (ER and Human Epidermal Receptor Growth Factor 2 (HER2, was per-formed on 168 samples from a breast cancer case series. The criteria for identifying women at high risk were based on those of the Breast Cancer Linkage Consortium. RESULTS: Familial tumors were more frequently positive for the p-cadherin (p = 0.0004, p63 (p < 0.0001 and CK5 (p < 0.0001 than was sporadic cancer. Moreover, familial tumors had coexpression of the basal biomarkers CK5+/ p63+, grouped two by two (OR = 34.34, while absence of coexpression (OR = 0.13 was associ-ated with the sporadic cancer phenotype. CONCLUSION: Familial breast cancer was found to be associated with basal biomarkers, using tissue microarray technology. Therefore, characterization of the familial breast cancer phenotype will improve the understanding of breast carcinogenesis.

  13. A biophysical model of the cortex-basal ganglia-thalamus network in the 6-OHDA lesioned rat model of Parkinson's disease.

    Science.gov (United States)

    Kumaravelu, Karthik; Brocker, David T; Grill, Warren M

    2016-04-01

    Electrical stimulation of sub-cortical brain regions (the basal ganglia), known as deep brain stimulation (DBS), is an effective treatment for Parkinson's disease (PD). Chronic high frequency (HF) DBS in the subthalamic nucleus (STN) or globus pallidus interna (GPi) reduces motor symptoms including bradykinesia and tremor in patients with PD, but the therapeutic mechanisms of DBS are not fully understood. We developed a biophysical network model comprising of the closed loop cortical-basal ganglia-thalamus circuit representing the healthy and parkinsonian rat brain. The network properties of the model were validated by comparing responses evoked in basal ganglia (BG) nuclei by cortical (CTX) stimulation to published experimental results. A key emergent property of the model was generation of low-frequency network oscillations. Consistent with their putative pathological role, low-frequency oscillations in model BG neurons were exaggerated in the parkinsonian state compared to the healthy condition. We used the model to quantify the effectiveness of STN DBS at different frequencies in suppressing low-frequency oscillatory activity in GPi. Frequencies less than 40 Hz were ineffective, low-frequency oscillatory power decreased gradually for frequencies between 50 Hz and 130 Hz, and saturated at frequencies higher than 150 Hz. HF STN DBS suppressed pathological oscillations in GPe/GPi both by exciting and inhibiting the firing in GPe/GPi neurons, and the number of GPe/GPi neurons influenced was greater for HF stimulation than low-frequency stimulation. Similar to the frequency dependent suppression of pathological oscillations, STN DBS also normalized the abnormal GPi spiking activity evoked by CTX stimulation in a frequency dependent fashion with HF being the most effective. Therefore, therapeutic HF STN DBS effectively suppresses pathological activity by influencing the activity of a greater proportion of neurons in the output nucleus of the BG.

  14. Usefulness of (18)F-FDG PET/CT in recurrent basal cell carcinoma: Report of a case.

    Science.gov (United States)

    Ayala, S; Perlaza, P; Puig, S; Prats, E; Vidal-Sicart, S

    2016-01-01

    We analyze the case of a patient with left periorbital infiltrating basal cell carcinoma treated with surgical excision in October 2010. Surgery included orbital exenteration and reconstruction using skin graft and radiotherapy. In May 2013 a MR imaging showed a mass in the left orbital fossa, suggesting a recurrence in the graft. A basal cell carcinoma recurrence with perineural invasion was confirmed in the biopsy. On (18)F-FDG PET/CT performed, a hypermetabolic activity was observed in the left periorbital area with extension to surrounding sinus and bones. The use of (18)F-FDG PET/CT in patients with advanced basal cell carcinoma has not been fully explored due to the rarity of this entity. This case demonstrates the usefulness of this technique to determine the extent of non-melanocytic recurrent skin tumors, and its value in the staging and treatment control, supporting the incorporation of (18)F-FDG PET/CT in the management of advanced basal cell carcinoma. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

  15. A Pause-then-Cancel model of stopping: evidence from basal ganglia neurophysiology.

    Science.gov (United States)

    Schmidt, Robert; Berke, Joshua D

    2017-04-19

    Many studies have implicated the basal ganglia in the suppression of action impulses ('stopping'). Here, we discuss recent neurophysiological evidence that distinct hypothesized processes involved in action preparation and cancellation can be mapped onto distinct basal ganglia cell types and pathways. We examine how movement-related activity in the striatum is related to a 'Go' process and how going may be modulated by brief epochs of beta oscillations. We then describe how, rather than a unitary 'Stop' process, there appear to be separate, complementary 'Pause' and 'Cancel' mechanisms. We discuss the implications of these stopping subprocesses for the interpretation of the stop-signal reaction time-in particular, some activity that seems too slow to causally contribute to stopping when assuming a single Stop processes may actually be fast enough under a Pause-then-Cancel model. Finally, we suggest that combining complementary neural mechanisms that emphasize speed or accuracy respectively may serve more generally to optimize speed-accuracy trade-offs.This article is part of the themed issue 'Movement suppression: brain mechanisms for stopping and stillness'. © 2017 The Author(s).

  16. Basal Serum Calcitonin, After Calcium Stimulation, and in the Needle Washout of Patients with Thyroid Nodules and Mild or Moderate Basal Hypercalcitoninemia.

    Science.gov (United States)

    Rosario, P W; Calsolari, M R

    2017-02-01

    This prospective study evaluated the concentrations of basal serum calcitonin (Ctn), Ctn after stimulation with calcium, and Ctn in the needle washout (FNA-Ctn) as predictors of sporadic medullary thyroid carcinoma (MTC) in patients with thyroid nodules and basal Ctn between 10 and 100 pg/ml. Forty-one patients were included in the study. MTC was diagnosed in only 6 patients (14.6%). None of the patients with basal Ctn≤24.6 pg/ml (n=26) or stimulated Ctn≤186.5 pg/ml (n=21) had MTC. All patients without MTC had basal Ctnstimulated Ctnbasal Ctn between 24.6 and 47 pg/ml (n=12), 3 (25%) had MTC. Among patients with stimulated Ctn between 186.5 and 655.2 pg/ml (n=18), 4 (22.2%) had MTC. FNA-Ctn distinguished nodules that were MTC (n=6) from those that were not (n=60), without overlapping results. In the calcium stimulation test, 19 patients (46.3%) reported some adverse effect, but none of them was severe or required specific treatment. Our results highlight that in patients without a history suspicious for MTC, mild or moderate basal hypercalcitoninemia should not establish the diagnosis of this tumor. Depending on the concentration found, basal Ctn should be sufficient to define patient management. In doubtful cases, FNA-Ctn seems to be the best diagnostic test. Calcium stimulation testing was safe, but more studies are needed to determine the Ctn cutoff after stimulation with calcium. © Georg Thieme Verlag KG Stuttgart · New York.

  17. Basal ganglia dysfunction in idiopathic REM sleep behaviour disorder parallels that in early Parkinson’s disease

    Science.gov (United States)

    Rolinski, Michal; Griffanti, Ludovica; Piccini, Paola; Roussakis, Andreas A.; Szewczyk-Krolikowski, Konrad; Menke, Ricarda A.; Quinnell, Timothy; Zaiwalla, Zenobia; Klein, Johannes C.; Mackay, Clare E.

    2016-01-01

    Abstract See Postuma (doi:10.1093/aww131) for a scientific commentary on this article. Resting state functional magnetic resonance imaging dysfunction within the basal ganglia network is a feature of early Parkinson’s disease and may be a diagnostic biomarker of basal ganglia dysfunction. Currently, it is unclear whether these changes are present in so-called idiopathic rapid eye movement sleep behaviour disorder, a condition associated with a high rate of future conversion to Parkinson’s disease. In this study, we explore the utility of resting state functional magnetic resonance imaging to detect basal ganglia network dysfunction in rapid eye movement sleep behaviour disorder. We compare these data to a set of healthy control subjects, and to a set of patients with established early Parkinson’s disease. Furthermore, we explore the relationship between resting state functional magnetic resonance imaging basal ganglia network dysfunction and loss of dopaminergic neurons assessed with dopamine transporter single photon emission computerized tomography, and perform morphometric analyses to assess grey matter loss. Twenty-six patients with polysomnographically-established rapid eye movement sleep behaviour disorder, 48 patients with Parkinson’s disease and 23 healthy control subjects were included in this study. Resting state networks were isolated from task-free functional magnetic resonance imaging data using dual regression with a template derived from a separate cohort of 80 elderly healthy control participants. Resting state functional magnetic resonance imaging parameter estimates were extracted from the study subjects in the basal ganglia network. In addition, eight patients with rapid eye movement sleep behaviour disorder, 10 with Parkinson’s disease and 10 control subjects received 123I-ioflupane single photon emission computerized tomography. We tested for reduction of basal ganglia network connectivity, and for loss of tracer uptake in rapid eye

  18. Lipid-rich histology in a basal-type immunoprofile breast carcinoma: histochemical and immunohistochemical analysis of a case

    Directory of Open Access Journals (Sweden)

    Francesco Maria Maiello

    2009-12-01

    Full Text Available We describe the clinicopathological and morphological features of an unusual breast carcinoma classifiable as a lipid-rich variant of ductal invasive carcinoma, with a basal-type immunohistochemical profile. Basal-type breast cancers show no hormonal receptor expression, rarely over-express HER-2 but exhibit molecular high weight cytokeratins, EGFR and c-kit positivity. Special stains and histochemistry tests were used to elucidate the nature of vescicles in the neoplastic cells. Sudan IV was performed on formalin-fixed tissue. Commercially available antibodies tested were: ER, PgR, EGFR, HER2, c-kit, high molecular weight cytokeratins. Cytoplasmic lipids were highlighted as red-orange droplets on Sudan IV staining. As for immunohistochemistry, the tumor showed no reactivity to ER, PgR and HER2 (triple negative, and diffuse and strong positivity to high weight cytokeratins, EGFR and c-kit, such as a basal-type breast carcinoma. A basaloid phenotype in a lipid-rich carcinoma has not been previously reported.

  19. A single splice site mutation in human-specific ARHGAP11B causes basal progenitor amplification

    Science.gov (United States)

    Florio, Marta; Namba, Takashi; Pääbo, Svante; Hiller, Michael; Huttner, Wieland B.

    2016-01-01

    The gene ARHGAP11B promotes basal progenitor amplification and is implicated in neocortex expansion. It arose on the human evolutionary lineage by partial duplication of ARHGAP11A, which encodes a Rho guanosine triphosphatase–activating protein (RhoGAP). However, a lack of 55 nucleotides in ARHGAP11B mRNA leads to loss of RhoGAP activity by GAP domain truncation and addition of a human-specific carboxy-terminal amino acid sequence. We show that these 55 nucleotides are deleted by mRNA splicing due to a single C→G substitution that creates a novel splice donor site. We reconstructed an ancestral ARHGAP11B complementary DNA without this substitution. Ancestral ARHGAP11B exhibits RhoGAP activity but has no ability to increase basal progenitors during neocortex development. Hence, a single nucleotide substitution underlies the specific properties of ARHGAP11B that likely contributed to the evolutionary expansion of the human neocortex. PMID:27957544

  20. Use of basal stimulation at anesthesiology department

    OpenAIRE

    MARKOVÁ, Alena

    2012-01-01

    The theme ?The Use of Basal Stimulation at the Anaesthesiology and Resuscitation Department? was chosen in order to map out the use of this nursing method by the nurses and the staff who I cooperate with. The theoretical part deals with the environment at the Anaesthesiology and Resuscitation Department where the basal stimulation is used and also with special characteristics of the nursing care. Further, it deals with monitoring patients, causes of consciousness defects occurrence and kinds ...

  1. The Development of the Basal Ganglia in Capuchin Monkeys (Cebus apella)

    Science.gov (United States)

    Phillips, Kimberley A.; Sobieski, Courtney A.; Gilbert, Valerie R.; Chiappini-Williamson, Christine; Sherwood, Chet C.; Strick, Peter L.

    2010-01-01

    The basal ganglia are subcortical structures involved in the planning, initiation and regulation of movement as well as a variety of non-motor, cognitive and affective functions. Capuchin monkeys share several important characteristics of development with humans, including a prolonged infancy and juvenile period, a long lifespan, and complex manipulative abilities. This makes capuchins important comparative models for understanding age-related neuroanatomical changes in these structures. Here we report developmental volumetric data on the three subdivisions of the basal ganglia, the caudate, putamen and globus pallidus in brown capuchin monkeys (Cebus apella). Based on a cross-sectional sample, we describe brain development in 28 brown capuchin monkeys (male n = 17, female n = 11; age range = 2 months – 20 years) using high-resolution structural MRI. We found that the raw volumes of the putamen and caudate varied significantly with age, decreasing in volume from birth through early adulthood. Notably, developmental changes did not differ between sexes. Because these observed developmental patterns are similar to humans, our results suggest that capuchin monkeys may be useful animal models for investigating neurodevelopmental disorders of the basal ganglia. PMID:20227397

  2. Reliability of basal plasma vasopressin concentrations in healthy male adults.

    Science.gov (United States)

    Quintana, Daniel S; Westlye, Lars T; Smerud, Knut T; Mahmoud, Ramy A; Djupesland, Per G; Andreassen, Ole A

    2017-10-01

    The neuropeptides oxytocin (OT) and arginine vasopressin (AVP) play important and interrelated roles in modulating mammalian social behaviour. While the OT system has received considerable research attention for its potential to treat psychiatric symptoms, comparatively little is known about the role of the AVP system in human social behaviour. To better understand the intraindividual stability of basal AVP, the present study assessed the reproducibility of basal plasma AVP concentrations. Basal plasma AVP was assessed at four sampling points separated by 8 days, on average, in 16 healthy adult males. Only one out of six comparisons revealed strong evidence for reproducibility of basal AVP concentrations (visit 2 vs. visit 4: r=0.8, p0.1). The concordance correlation coefficient [0.15, 95% CI (-0.55, 0.73)] also revealed poor overall reproducibility. Poor reliability of basal AVP concentrations suggests future work covarying AVP with trait markers should proceed with careful consideration of intraindividual fluctuations.

  3. Photosynthate partitioning in basal zones of tall fescue leaf blades

    International Nuclear Information System (INIS)

    Allard, G.; Nelson, C.J.

    1991-01-01

    Elongating grass leaves have successive zones of cell division, cell elongation, and cell maturation in the basal portion of the blade and are a strong sink for photosynthate. Our objective was to determine dry matter (DM) deposition and partitioning in basal zones of elongating tall fescue (Festuca arundinacea Schreb.) leaf blades. Vegetative tall fescue plants were grown in continuous light (350 micromoles per square meter per second photosynthetic photon flux density) to obtain a constant spatial distribution of elongation growth with time. Content and net deposition rates of water-soluble carbohydrates (WSC) and DM along elongating leaf blades were determined. These data were compared with accumulation of 14 C in the basal zones following leaf-labeling with 14 CO 2 . Net deposition of DM was highest in the active cell elongation zone, due mainly to deposition of WSC. The maturation zone, just distal to the elongation zone, accounted for 22% of total net deposition of DM in elongating leaves. However, the spatial profile of 14 C accumulation suggested that the elongation zone and the maturation zone were sinks of equal strength. WSC-free DM accounted for 55% of the total net DM deposition in elongating leaf blades, but only 10% of incoming 14 C-photosynthate accumulated in the water-insoluble fraction (WIF ∼ WSC-free DM) after 2 hours. In the maturation zone, more WSC was used for synthesis of WSC-free DM than was imported as recent photosynthate

  4. Basal Cell Carcinoma of the Dorsal Foot: An Update and Comprehensive Review of the Literature.

    Science.gov (United States)

    Loh, Tiffany Y; Rubin, Ashley G; Jiang, Shang I Brian

    2017-01-01

    Ultraviolet radiation is a well-known risk factor for basal cell carcinoma (BCC). Therefore, the high incidence of BCCs in sun-exposed areas such as the head and neck is unsurprising. However, unexpectedly, BCCs on the sun-protected dorsal foot have also been reported, and tumor occurrence here suggests that other factors besides ultraviolet radiation may play a role in BCC pathogenesis. Because only few dorsal foot BCCs have been reported, data on their clinical features and management are limited. To perform an updated review of the literature on clinical characteristics and treatment of dorsal foot BCCs. We conducted a comprehensive literature review by searching the PubMed database with the key phrases "basal cell carcinoma dorsal foot," "basal cell carcinoma foot," and "basal cell carcinoma toe." We identified 20 cases of dorsal foot BCCs in the literature, 17 of which had sufficient data for analysis. Only 1 case was treated with Mohs micrographic surgery. We present 8 additional cases of dorsal foot BCCs treated with Mohs micrographic surgery. Basal cell carcinomas on the dorsal foot are rare, and potential risk factors include Caucasian descent and personal history of skin cancer. Mohs micrographic surgery seems to be an effective treatment option.

  5. Effects of short-term hormonal replacement on learning and on basal forebrain ChAT and TrkA content in ovariectomized rats.

    Science.gov (United States)

    Espinosa-Raya, Judith; Plata-Cruz, Noemí; Neri-Gómez, Teresa; Camacho-Arroyo, Ignacio; Picazo, Ofir

    2011-02-23

    It has been proposed that sex steroid hormones improve performance in some cognitive tasks by regulating the basal forebrain cholinergic function. However, the molecular basis of such influence still remains unknown. Current study analyzed the performance of ovariectomized rats in an autoshaping learning task after a short-term treatment with 17β-estradiol (E2: 4 and 40μg/kg) and/or progesterone (P4: 4mg/kg). These results were correlated with basal forebrain choline acetyltransferase (ChAT) and TrkA protein content. The high dose of E2 enhanced both acquisition in the autoshaping task and the content of ChAT and TrkA. P4 treatment increased ChAT and TrkA content without affecting performance of rats in the autoshaping learning task. Interestingly, the continuous and simultaneous administration of E2 plus P4 did not significantly modify behavioral and biochemical evaluated parameters. These results address the influence of both E2 and P4 on cholinergic and TrkA activity and suggest that the effects of ovarian hormones on cognitive performance involve basal forebrain cholinergic neurons. Copyright © 2010 Elsevier B.V. All rights reserved.

  6. Thermal history regulates methylbutenol basal emission rate in Pinus ponderosa.

    Science.gov (United States)

    Gray, Dennis W; Goldstein, Allen H; Lerdau, Manuel T

    2006-07-01

    Methylbutenol (MBO) is a 5-carbon alcohol that is emitted by many pines in western North America, which may have important impacts on the tropospheric chemistry of this region. In this study, we document seasonal changes in basal MBO emission rates and test several models predicting these changes based on thermal history. These models represent extensions of the ISO G93 model that add a correction factor C(basal), allowing MBO basal emission rates to change as a function of thermal history. These models also allow the calculation of a new emission parameter E(standard30), which represents the inherent capacity of a plant to produce MBO, independent of current or past environmental conditions. Most single-component models exhibited large departures in early and late season, and predicted day-to-day changes in basal emission rate with temporal offsets of up to 3 d relative to measured basal emission rates. Adding a second variable describing thermal history at a longer time scale improved early and late season model performance while retaining the day-to-day performance of the parent single-component model. Out of the models tested, the T(amb),T(max7) model exhibited the best combination of day-to-day and seasonal predictions of basal MBO emission rates.

  7. Basal cell epithelioma (carcinoma) in children and teenagers

    Energy Technology Data Exchange (ETDEWEB)

    Rahbari, H.; Mehregan, A.H.

    1982-01-15

    Among over 390,000 routine dermatopathologic specimens there were 85 cases diagnosed as basal cell epithelioma (carcinoma) (BCE) in persons 19 years old or younger. This number was refined to 40 cases de novo BCE in children and teenagers. Basal cell epithelioma unrelated to other conditions is rare in the young and it should be differentiated from similar fibroepithelial growths.

  8. Genetic analysis of partial resistance to basal stem rot (Sclerotinia sclerotiorum in sunflower

    Directory of Open Access Journals (Sweden)

    Amouzadeh Masoumeh

    2013-01-01

    Full Text Available Basal stem rot, caused by Sclerotinia sclerotiorum (Lib. de Bary, is one of the major diseases of sunflower (Helianthus annuus L. in the world. Quantitative trait loci (QTLs implicated in partial resistance to basal stem rot disease were identified using 99 recombinant inbred lines (RILs from the cross between sunflower parental lines PAC2 and RHA266. The study was undertaken in a completely randomized design with three replications under controlled conditions. The RILs and their parental lines were inoculated with a moderately aggressive isolate of S. sclerotiorum (SSKH41. Resistance to disease was evaluated by measuring the percentage of necrosis area three days after inoculation. QTLs were mapped using an updated high-density SSR and SNP linkage map. ANOVA showed significant differences among sunflower lines for resistance to basal stem rot (P≤0.05. The frequency distribution of lines for susceptibility to disease showed a continuous pattern. Composite interval mapping analysis revealed 5 QTLs for percentage of necrotic area, localized on linkage groups 1, 3, 8, 10 and 17. The sign of additive effect was positive in 5 QTLs, suggesting that the additive allele for partial resistance to basal stem rot came from the paternal line (RHA266. The phenotypic variance explained by QTLs (R2 ranged from 0.5 to 3.16%. Identified genes (HUCL02246_1, GST and POD, and SSR markers (ORS338, and SSL3 encompassing the QTLs for partial resistance to basal stem rot could be good candidates for marker assisted selection.

  9. Fissura palatina reparada: fechamento velofaríngeo antes e durante o som basal Cleft palate repair: velopharyngeal closure before and during the basal tone

    Directory of Open Access Journals (Sweden)

    Giseane Conterno

    2010-04-01

    Full Text Available Portadores de fissura palatina apresentam inadequado fechamento velofaríngeo (FVF, com consequente hipernasalidade vocal que pode ser diminuída com o som basal. OBJETIVO: Comparar o FVF durante a realização do som basal com a emissão em registro modal, em pacientes com fissura palatina pós-forame reparada. MATERIAIS E MÉTODOS: Estudo de Casos com quatro homens adultos, portadores de fissura palatina pós-forame reparada. Imagens do FVF por nasofaringoscopia, durante a emissão da vogal [a] em registro modal e basal. Julgamento das imagens realizado por quatro otorrinolaringologistas. RESULTADOS: Em três sujeitos, não houve mudança no tipo de FVF entre os registros analisados; as modificações que ocorreram na maioria dos sujeitos referem-se apenas ao grau de movimentação das estruturas envolvidas, pois, em registro basal, o movimento das paredes laterais da faringe se manteve, o movimento da parede posterior da faringe estabilizou, o movimento do véu palatino diminuiu discretamente, e a Prega de Passavant se evidenciou. CONCLUSÕES: O tipo de FVF se manteve em três dos quatro sujeitos analisados, quando comparado o registro modal com o basal, havendo modificações no grau da movimentação das estruturas envolvidas, evidenciando a Prega de Passavant.Patients with palatine fissure have inadequate velopharyngeal closure (VPC, with consequent vocal hypernasality which can be reduced by a basal tone. AIM: to compare VPC during a basal tone with the emission of a modal recording, in patients with repaired post-foramen palatine fissure. MATERIALS AND METHODS: case study with four adult men, all with repaired post-foramen palatine fissure. VPC images through nasal-pharyngoscopy during the emission o f the [a] vowel in a modal and basal recording. The images were studied by four ENTs. RESULTS: in three subjects there was no change in the type of VPC considering the recordings analyzed; the changes which happened to most of the subjects

  10. Dopamine-dependent changes in the functional connectivity between basal ganglia and cerebral cortex in humans

    NARCIS (Netherlands)

    Williams, D; Tijssen, M; van Bruggen, G; Bosch, A; Insola, A; Di Lazzaro, V; Mazzone, P; Oliviero, A; Quartarone, A; Speelman, H; Brown, P

    2002-01-01

    We test the hypothesis that interaction between the human basal ganglia and cerebral cortex involves activity in multiple functional circuits characterized by their frequency of oscillation, phase characteristics, dopamine dependency and topography. To this end we took recordings from

  11. Comprehensive in vivo mapping of the human basal ganglia and thalamic connectome in individuals using 7T MRI.

    Directory of Open Access Journals (Sweden)

    Christophe Lenglet

    Full Text Available Basal ganglia circuits are affected in neurological disorders such as Parkinson's disease (PD, essential tremor, dystonia and Tourette syndrome. Understanding the structural and functional connectivity of these circuits is critical for elucidating the mechanisms of the movement and neuropsychiatric disorders, and is vital for developing new therapeutic strategies such as deep brain stimulation (DBS. Knowledge about the connectivity of the human basal ganglia and thalamus has rapidly evolved over recent years through non-invasive imaging techniques, but has remained incomplete because of insufficient resolution and sensitivity of these techniques. Here, we present an imaging and computational protocol designed to generate a comprehensive in vivo and subject-specific, three-dimensional model of the structure and connections of the human basal ganglia. High-resolution structural and functional magnetic resonance images were acquired with a 7-Tesla magnet. Capitalizing on the enhanced signal-to-noise ratio (SNR and enriched contrast obtained at high-field MRI, detailed structural and connectivity representations of the human basal ganglia and thalamus were achieved. This unique combination of multiple imaging modalities enabled the in-vivo visualization of the individual human basal ganglia and thalamic nuclei, the reconstruction of seven white-matter pathways and their connectivity probability that, to date, have only been reported in animal studies, histologically, or group-averaged MRI population studies. Also described are subject-specific parcellations of the basal ganglia and thalamus into sub-territories based on their distinct connectivity patterns. These anatomical connectivity findings are supported by functional connectivity data derived from resting-state functional MRI (R-fMRI. This work demonstrates new capabilities for studying basal ganglia circuitry, and opens new avenues of investigation into the movement and neuropsychiatric

  12. Simulation of cortico-basal ganglia oscillations and their suppression by closed loop deep brain stimulation.

    Science.gov (United States)

    Grant, Peadar F; Lowery, Madeleine M

    2013-07-01

    A new model of deep brain stimulation (DBS) is presented that integrates volume conduction effects with a neural model of pathological beta-band oscillations in the cortico-basal ganglia network. The model is used to test the clinical hypothesis that closed-loop control of the amplitude of DBS may be possible, based on the average rectified value of beta-band oscillations in the local field potential. Simulation of closed-loop high-frequency DBS was shown to yield energy savings, with the magnitude of the energy saved dependent on the strength of coupling between the subthalamic nucleus and the remainder of the cortico-basal ganglia network. When closed-loop DBS was applied to a strongly coupled cortico-basal ganglia network, the stimulation energy delivered over a 480 s period was reduced by up to 42%. Greater energy reductions were observed for weakly coupled networks, as the stimulation amplitude reduced to zero once the initial desynchronization had occurred. The results provide support for the application of closed-loop high-frequency DBS based on electrophysiological biomarkers.

  13. Immune defense of wild-caught Norway rats is characterized by increased levels of basal activity but reduced capability to respond to further immune stimulation.

    Science.gov (United States)

    Mirkov, Ivana; Popov Aleksandrov, Aleksandra; Subota, Vesna; Kataranovski, Dragan; Kataranovski, Milena

    2018-03-01

    Studies of wild animals' immunity often use comparison with laboratory-raised individuals. Using such an approach, various data were obtained concerning wild Norway rat's immunity. Lower or higher potential of immune system cells to respond to activation stimuli were shown, because of analysis of disparate parameters and/ or small number of analyzed individuals. Inconsistent differences between laboratory and wild rats were shown too, owing to great response variability in wild rats. We hypothesized that wild rats will express more intense immune activity compared to their laboratory counterparts which live in a less demanding environment. To test this, we analyzed the circulating levels of inflammatory cytokine interleukin-6 (IL-6), a mediator which has a central role in host immune defense. In addition, we examined the activity of the central immune organ, the spleen, including cell proliferation and production of pro-inflammatory cytokines interferon-γ (IFN-γ) and interleukin-17 (IL-17), which are major effectors of cellular adaptive immune response. In order to obtain reasonable insight into the immunity of wild Norway rats, analysis was conducted on a much larger number of individuals compared to other studies. Higher levels of plasma IL-6, higher spleen mass, cellularity and basal IFN-γ production concomitantly with lower basal production of anti-inflammatory cytokine interleukin-10 (IL-10) revealed more intense immune activity in the wild compared to laboratory rats. However, lower responsiveness of their spleen cells' proinflammatory cytokine production to concanavalin A (ConA) stimulation, along with preserved capacity of IL-10 response, might be perceived as an indication of wild rats' reduced capability to cope with incoming environmental stimuli, but also as a means to limit tissue damage. © 2017 International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.

  14. 1H MR spectroscopy of the basal ganglia in childhood: a semiquantitative analysis

    International Nuclear Information System (INIS)

    Lam, W.W.M.; Zhao, H.; Berry, G.T.; Kaplan, P.; Gibson, J.; Kaplan, B.S.

    1998-01-01

    Proton MR spectra of the basal ganglia were obtained from 28 patients, 24 male and 14 female, median age 16.3 months (5 weeks to 31 years). They included 17 patients with normal MRI of the basal ganglia without metabolic disturbance (control group) and 11 patients with various metabolic diseases: one case each of high serum sodium and high serum osmolarity, cobalamin C deficiency, Leigh disease, Galloway-Mowat syndrome, Pelizaeus-Merzbacher disease, hemolytic-uremic syndrome and Wilson disease and two cases of Alagille syndrome and methylmalonic acidemia with abnormal MRI of the basal ganglia or blood or urine analysis (abnormal group). The MR spectrum was measured by using STEAM. The MR-visible water content of the region of interest was obtained. Levels of myoinositol, choline, creatine and N -acetylaspartate were measured using a semiquantitative approach, with absolute reference calibration. In the control group, there was a gradual drop of water content over the first year of life; N -acetylaspartate, creatine and myoinositol levels showed no significant change with age, in contrast to the occipital, parietal and cerebellar regions. Choline showed a gradual decrease for the first 2 years of life and then remained fairly constant. In the abnormal group the water content was not significantly different. N -Acetylaspartate was decreased in patients with high serum sodium and high serum osmolarity, cobalamin C deficiency, Leigh disease and one case of methylmalonic acidemia. Decreased creatine was also found in Leigh disease, and decreased choline in Galloway-Mowat syndrome and Wilson disease. Myoinositol was elevated in the patient with abnormally high serum sodium, and decreased in the hemolytic-uremic syndrome. (orig.)

  15. Diagnosis, balances and energy indicators in municipalities of 'BASAL' project

    International Nuclear Information System (INIS)

    Pérez Martín, David; Soler Iglesias, Belkis; López López, Ileana; Moreno, Helsy; Matos, Yamilexis; Sanfiel, Caridad; Román, José Enrique

    2015-01-01

    Under the 'Basis for Environmental Sustainability Local Food' project (BASAL)) transverse energy-related activities were conducted. In this work we are analyzed and presented energy diagnoses in municipalities Los Palacios, Guira de Melena and Jimaguayú, capturing energy statistics in the 3 municipalities, energy balances and key energy indicators compared to support sustainability and decision making. (full text)

  16. Disparate effects of non-steroidal anti-inflammatory drugs on apoptosis in guinea-pig gastric mucous cells: inhibition of basal apoptosis by diclofenac

    Science.gov (United States)

    Ashton, Miranda; Hanson, Peter J

    2002-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) induce apoptosis in gastrointestinal cancer cell lines. Similar actions on normal gastric epithelial cells could contribute to NSAID gastropathy. The present work therefore compared the actions of diclofenac, ibuprofen, indomethacin, and the cyclo-oxygenase-2 selective inhibitor, NS-398, on a primary culture of guinea-pig gastric mucous epithelial cells. Cell number was assessed by staining with crystal violet. Apoptotic activity was determined by condensation and fragmentation of nuclei and by assay of caspase-3-like activity. Necrosis was evaluated from release of cellular enzymes. Ibuprofen (250 μM for 24 h) promoted cell loss, and apoptosis, under both basal conditions and when apoptosis was increased by 25 μM N-Hexanoyl-D-sphingosine (C6-ceramide). Diclofenac (250 μM for 24 h) reduced the proportion of apoptotic nuclei from 5.2 to 2.1%, and caused inhibition of caspase-3-like activity, without causing necrosis under basal conditions. No such reduction in apoptotic activity was evident in the presence of 25 μM C6-ceramide. The inhibitory effect of diclofenac on basal caspase-3-like activity was also exhibited by the structurally similar mefenamic and flufenamic acids (1–250 μM), but not by niflumic acid. Inhibition of superoxide production by the cells increased caspase-3-like activity, but the inhibitory action of diclofenac on caspase activity remained. Diclofenac did not affect superoxide production. Diclofenac inhibited caspase-3-like activity in cell homogenates and also inhibited human recombinant caspase-3. In conclusion, NSAIDs vary in their effect on apoptotic activity in a primary culture of guinea-pig gastric mucous epithelial cells, and the inhibitory effect of diclofenac on basal apoptosis could involve an action on caspase activity. PMID:11815376

  17. The relationship between basal metabolic rate and daily energy expenditure in birds and mammals

    NARCIS (Netherlands)

    Ricklefs, RE; Konarzewski, M; Daan, S

    We examined the relationship between daily energy expenditure (DEE) and basal metabolic rate (BMR) in birds and mammals. Two models of the relationship between DEE and BMR were distinguished: a ''shared pathways'' model in which DEE replaces BMR in the active organism and a ''partitioned pathways''

  18. CT cisternography of the basal cisterns

    International Nuclear Information System (INIS)

    Galanski, M.; Dickob, M.; Wittkowski, W.; Muenster Univ.

    1986-01-01

    Air cisternograms at post mortem and positive contrast cisternograms on patients were performed in order to study intracisternal structures, particularly cranial nerves, as seen on CT. Air and contrast CT cisternograms showed excellent demonstration of the second, third, fifth, sixth, seventh and eighth cranial nerves. The ninth and tenth cranial nerves could not always be separated from each other and demonstration of the first, fourth, eleventh and twelfth cranial nerves was often not possible or was unsatisfactory. With a knowledge of the normal anatomy and of important surrounding structures, the individual cranial nerves are easily identified. The anthropologic baseline appears highly suitable for CT examination of the basal cisterns. The complementary coronal projection is also very valuable. (orig.) [de

  19. Vismodegib (ERIVEDGE°) In basal cell carcinoma: too many unknowns.

    Science.gov (United States)

    2015-01-01

    Basal cell carcinomas are the most common skin cancers. They are usually localised and carry a good prognosis. There is no standard treatment for the rare patients with metastatic basal cell carcinoma or very extensive basal cell carcinoma for whom surgery or radiotherapy is inappropriate. Vismodegib, a cytotoxic drug, is claimed to prevent tumour growth by inhibiting a pathway involved in tissue repair and embryogenesis. It has been authorised in the European Union for patients with metastatic or locally advanced and extensive basal cell carcinoma. Clinical evaluation of vismodegib is based on a non-comparative clinical trial involving 104 patients, providing only weak evidence. Twenty-one months after the start of the trial, 7 patients with metastases (21%) and 6 patients with advanced basal cell carcinoma (10%) had died. Given the lack of a placebo group, there is no way of knowing whether vismodegib had any effect, positive or negative, on survival. There were no complete responses among patients with metastases, but about one-third of them had partial responses. Among the 63 patients with locally advanced basal cell carcinoma, there were 14 complete responses and 16 partial responses. The recurrence rate in patients with complete responses was not reported. Similar results were reported in two other uncontrolled trials available in mid-2014. Vismodegib has frequent and sometimes serious adverse effects, including muscle spasms, fatigue and severe hyponatraemia. Cases of severe weight loss, alopecia, ocular disorders, other cancers (including squamous cell carcinoma) and anaemia have also been reported. More data are needed on possible hepatic and cardiovascular adverse effects. A potent teratogenic effect was seen in experimental animals. As vismodegib enters semen, contraception is mandatory for both men (condoms) and women. In practice, vismodegib has frequent and varied adverse effects, some of which are serious, while its benefits are poorly documented

  20. Parallel basal ganglia circuits for decision making.

    Science.gov (United States)

    Hikosaka, Okihide; Ghazizadeh, Ali; Griggs, Whitney; Amita, Hidetoshi

    2018-03-01

    The basal ganglia control body movements, mainly, based on their values. Critical for this mechanism is dopamine neurons, which sends unpredicted value signals, mainly, to the striatum. This mechanism enables animals to change their behaviors flexibly, eventually choosing a valuable behavior. However, this may not be the best behavior, because the flexible choice is focused on recent, and, therefore, limited, experiences (i.e., short-term memories). Our old and recent studies suggest that the basal ganglia contain separate circuits that process value signals in a completely different manner. They are insensitive to recent changes in value, yet gradually accumulate the value of each behavior (i.e., movement or object choice). These stable circuits eventually encode values of many behaviors and then retain the value signals for a long time (i.e., long-term memories). They are innervated by a separate group of dopamine neurons that retain value signals, even when no reward is predicted. Importantly, the stable circuits can control motor behaviors (e.g., hand or eye) quickly and precisely, which allows animals to automatically acquire valuable outcomes based on historical life experiences. These behaviors would be called 'skills', which are crucial for survival. The stable circuits are localized in the posterior part of the basal ganglia, separately from the flexible circuits located in the anterior part. To summarize, the flexible and stable circuits in the basal ganglia, working together but independently, enable animals (and humans) to reach valuable goals in various contexts.

  1. Sp1/Sp3 and DNA-methylation contribute to basal transcriptional activation of human podoplanin in MG63 versus Saos-2 osteoblastic cells

    Directory of Open Access Journals (Sweden)

    Puri Christina

    2007-03-01

    , treatment with the DNA methyltransferase inhibitor 5-azaCdR in combination with trichostatin A (TSA downregulated podoplanin mRNA levels in MG63 cells, and region-specific in vitro methylation of the distal promoter suggested that DNA methylation rather enhanced than hindered PDPN transcription in both cell types. Conclusion These data establish that in human osteoblast-like MG63 cells, Sp1 and Sp3 stimulate basal PDPN transcription in a concerted, yet independent manner, whereas Saos-2 cells lack sufficient nuclear Sp protein amounts for transcriptional activation. Moreover, a highly methylated chromatin conformation of the distal promoter region confers cell-type specific podoplanin upregulation versus Saos-2 cells.

  2. Computational Stimulation of the Basal Ganglia Neurons with Cost Effective Delayed Gaussian Waveforms.

    Science.gov (United States)

    Daneshzand, Mohammad; Faezipour, Miad; Barkana, Buket D

    2017-01-01

    Deep brain stimulation (DBS) has compelling results in the desynchronization of the basal ganglia neuronal activities and thus, is used in treating the motor symptoms of Parkinson's disease (PD). Accurate definition of DBS waveform parameters could avert tissue or electrode damage, increase the neuronal activity and reduce energy cost which will prolong the battery life, hence avoiding device replacement surgeries. This study considers the use of a charge balanced Gaussian waveform pattern as a method to disrupt the firing patterns of neuronal cell activity. A computational model was created to simulate ganglia cells and their interactions with thalamic neurons. From the model, we investigated the effects of modified DBS pulse shapes and proposed a delay period between the cathodic and anodic parts of the charge balanced Gaussian waveform to desynchronize the firing patterns of the GPe and GPi cells. The results of the proposed Gaussian waveform with delay outperformed that of rectangular DBS waveforms used in in-vivo experiments. The Gaussian Delay Gaussian (GDG) waveforms achieved lower number of misses in eliciting action potential while having a lower amplitude and shorter length of delay compared to numerous different pulse shapes. The amount of energy consumed in the basal ganglia network due to GDG waveforms was dropped by 22% in comparison with charge balanced Gaussian waveforms without any delay between the cathodic and anodic parts and was also 60% lower than a rectangular charged balanced pulse with a delay between the cathodic and anodic parts of the waveform. Furthermore, by defining a Synchronization Level metric, we observed that the GDG waveform was able to reduce the synchronization of GPi neurons more effectively than any other waveform. The promising results of GDG waveforms in terms of eliciting action potential, desynchronization of the basal ganglia neurons and reduction of energy consumption can potentially enhance the performance of DBS

  3. Computational Stimulation of the Basal Ganglia Neurons with Cost Effective Delayed Gaussian Waveforms

    Directory of Open Access Journals (Sweden)

    Mohammad Daneshzand

    2017-08-01

    Full Text Available Deep brain stimulation (DBS has compelling results in the desynchronization of the basal ganglia neuronal activities and thus, is used in treating the motor symptoms of Parkinson's disease (PD. Accurate definition of DBS waveform parameters could avert tissue or electrode damage, increase the neuronal activity and reduce energy cost which will prolong the battery life, hence avoiding device replacement surgeries. This study considers the use of a charge balanced Gaussian waveform pattern as a method to disrupt the firing patterns of neuronal cell activity. A computational model was created to simulate ganglia cells and their interactions with thalamic neurons. From the model, we investigated the effects of modified DBS pulse shapes and proposed a delay period between the cathodic and anodic parts of the charge balanced Gaussian waveform to desynchronize the firing patterns of the GPe and GPi cells. The results of the proposed Gaussian waveform with delay outperformed that of rectangular DBS waveforms used in in-vivo experiments. The Gaussian Delay Gaussian (GDG waveforms achieved lower number of misses in eliciting action potential while having a lower amplitude and shorter length of delay compared to numerous different pulse shapes. The amount of energy consumed in the basal ganglia network due to GDG waveforms was dropped by 22% in comparison with charge balanced Gaussian waveforms without any delay between the cathodic and anodic parts and was also 60% lower than a rectangular charged balanced pulse with a delay between the cathodic and anodic parts of the waveform. Furthermore, by defining a Synchronization Level metric, we observed that the GDG waveform was able to reduce the synchronization of GPi neurons more effectively than any other waveform. The promising results of GDG waveforms in terms of eliciting action potential, desynchronization of the basal ganglia neurons and reduction of energy consumption can potentially enhance the

  4. Replacement of soybean oil by fish oil increases cytosolic lipases activities in liver and adipose tissue from rats fed a high-carbohydrate diets.

    Science.gov (United States)

    Rodrigues, Angélica Heringer; Moreira, Carolina Campos Lima; Neves, Maria José; Botion, Leida Maria; Chaves, Valéria Ernestânia

    2018-06-01

    Several studies have demonstrated that fish oil consumption improves metabolic syndrome and comorbidities, as insulin resistance, nonalcoholic fatty liver disease, dyslipidaemia and hypertension induced by high-fat diet ingestion. Previously, we demonstrated that administration of a fructose-rich diet to rats induces liver lipid accumulation, accompanied by a decrease in liver cytosolic lipases activities. In this study, the effect of replacement of soybean oil by fish oil in a high-fructose diet (FRUC, 60% fructose) for 8 weeks on lipid metabolism in liver and epididymal adipose tissue from rats was investigated. The interaction between fish oil and FRUC diet increased glucose tolerance and decreased serum levels of triacylglycerol (TAG), VLDL-TAG secretion and lipid droplet volume of hepatocytes. In addition, the fish oil supplementation increased the liver cytosolic lipases activities, independently of the type of carbohydrate ingested. Our results firmly establish the physiological regulation of liver cytosolic lipases to maintain lipid homeostasis in hepatocytes. In epididymal adipose tissue, the replacement of soybean oil by fish oil in FRUC diet did not change the tissue weight and lipoprotein lipase activity; however, there was increased basal and insulin-stimulated de novo lipogenesis and glucose uptake. Increased cytosolic lipases activities were observed, despite the decreased basal and isoproterenol-stimulated glycerol release to the incubation medium. These findings suggest that fish oil increases the glycerokinase activity and glycerol phosphorylation from endogenous TAG hydrolysis. Our findings are the first to show that the fish oil ingestion increases cytosolic lipases activities in liver and adipose tissue from rats treated with high-carbohydrate diets. Copyright © 2018. Published by Elsevier Inc.

  5. Effects of high fat diet on the basal activity of the hypothalamus- pituitary-adrenal axis in mice: A systematic review

    NARCIS (Netherlands)

    Auvinen, H.E.; Romijn, J.A.; Biermasz, N.R.; Havekes, L.M.; Smit, J.W.A.; Rensen, P.C.N.; Pereira, A.M.

    2011-01-01

    Hypothalamus-pituitary-adrenal-axis activity is suggested to be involved in the pathophysiology of the metabolic syndrome. In diet-induced obesity mouse models, features of the metabolic syndrome are induced by feeding high fat diet. However, the models reveal conflicting results with respect to the

  6. Nevoid basal cell carcinoma syndrome; Naevoid Basalzellkarzinom-Syndrom

    Energy Technology Data Exchange (ETDEWEB)

    Grgic, A.; Heinrich, M.; Heckmann, M.; Kramann, B. [Universitaetsklinikum des Saarlandes, Homburg/Saar (Germany). Abt. fuer Diagnostische und Interventionelle Radiologie; Aliani, S. [Universitaetsklinikum des Saarlandes, Homburg/Saar (Germany). Klinik fuer Kinder- und Jugendmedizin; Dill-Mueller, D. [Universitaetsklinikum des Saarlandes, Homburg/Saar (Germany). Hautklinik und Poliklinik; Uder, M. [Erlange-Nuernberg Univ. (Germany). Inst. fuer Diagnostische Radiologie

    2005-07-01

    Nevoid Basal Cell Carcinoma Syndrome (NBCCS) is an autosomal-dominant disorder characterized by multiple basal cell carcinomas, jaw cysts, palmar/plantar pits, calcification of the falx cerebri, and spine and rib anomalies. The combination of clinical, imaging, and histological findings is helpful in identifying NBCCS patients. Imaging plays a crucial role in evaluation of these patients. We present a wide variety of clinical and radiological findings characteristic of this disease. (orig.)

  7. Bilateral basal ganglia calcifications visualised on CT scan.

    OpenAIRE

    Brannan, T S; Burger, A A; Chaudhary, M Y

    1980-01-01

    Thirty-eight cases of basal ganglia calcification imaged on computed axial tomography were reviewed. Most cases were felt to represent senescent calcification. The possibility of a vascular aetiology in this group is discussed. A less common group of patients was identified with calcification secondary to abnormalities in calcium metabolism or radiation therapy. Three cases of basal ganglia calcifications were detected in juvenile epileptic patients receiving chronic anticonvulsants. These ca...

  8. A morphometric CT study of Down's syndrome showing small posterior fossa and calcification of basal ganglia

    International Nuclear Information System (INIS)

    Ieshima, A.; Yoshino, K.; Takashima, S.; Takeshita, K.; Kisa, T.

    1984-01-01

    We report characteristic and morphometric changes of cranial computed tomography (CT) with increasing age in 56 patients with Down's syndrome aged from 0 month to 37 years. Patients were compared with 142 normal controls aged 0 to 59 years. Width of ventricles, Sylvian fissures, posterior fossa, pons and cisterna magna were measured on CT. The incidences of the cavum septi pellucidi, cavum vergae and cavum veli interpositi and high density in the basal ganglia were examined. There was high incidence (10.7%) of bilateral calcification of basal ganglia in Down's syndrome, although that of pineal body and choroid plexus calcification was similar in Down's syndrome and controls. Basal ganglia calcification is more frequently seen in young Down's syndrome and may be related to the premature aging characteristic of Down's syndrome. The CT in Down's syndrome showed relatively small posterior fossa, small cerebellum, small brain stem and relatively large Sylvian fissures in those under one year of age. There was a high frequency of midline cava and large cisterna magna. There were no significant atrophic changes on CT except after the fifth decade comparing with controls. (orig.)

  9. Impact of the basal metabolic ratio in predicting early deaths after allogeneic stem cell transplantation.

    Science.gov (United States)

    Nishiwaki, Satoshi; Miyamura, Koichi; Seto, Aika; Watanabe, Keisuke; Yanagisawa, Mayumi; Imahashi, Nobuhiko; Shimba, Makoto; Yasuda, Takahiko; Kuwatsuka, Yachiyo; Oba, Taku; Terakura, Seitaro; Kodera, Yoshihisa

    2009-09-01

    Early deaths after allogeneic stem cell transplantation (allo-SCT) are of major concern. On the assumption that both decreased and increased basal metabolism might relate to early deaths, we analyzed the risk factors for overall survival to days 30 (OS30) and 60 (OS60). The Harris-Benedict equation was used to calculate basal metabolism. Comparing a patient's basal metabolism (PBM) calculated from pretransplant body weight with the standard basal metabolism (SBM) calculated from standard body weight (body mass index (BMI) = 22), we defined the basal metabolic ratio (BMR) as a parameter (BMR = PBM/SBM). We retrospectively analyzed 360 adult patients transplanted between 1997 and 2006 at a single center in Japan. A multivariate analysis of OS30 showed risk factors to be: BMR BMR; LBR) (P = 0.01), BMR > 1.05 (high BMR; HBR) (P = 0.005) and non-complete remission (non-CR) (P 5 0.001), whereas a multivariate analysis of OS60 showed those risk factors to be: LBR (P = 0.02), HBR (P = 0.04), non-CR (P = 0.002), and performance status BMR BMR; ABR) (96.8 and 90.3% for ABR, 87.1 and 76.2% for LBR, and 87.8 and 81.1% for HBR). In conclusion, BMR could prove to be a predictor of early death after allo-SCT.

  10. Basal testosterone, leadership and dominance: A field study and meta-analysis.

    Science.gov (United States)

    van der Meij, Leander; Schaveling, Jaap; van Vugt, Mark

    2016-10-01

    This article examines the role of basal testosterone as a potential biological marker of leadership and hierarchy in the workplace. First, we report the result of a study with a sample of male employees from different corporate organizations in the Netherlands (n=125). Results showed that employees with higher basal testosterone levels reported a more authoritarian leadership style, but this relationship was absent among those who currently held a real management position (i.e., they had at least one subordinate). Furthermore, basal testosterone levels were not different between managers and non-managers, and testosterone was not associated with various indicators of status and hierarchy such as number of subordinates, income, and position in the organizational hierarchy. In our meta-analysis (second study), we showed that basal testosterone levels were not associated with leadership in men nor in women (9 studies, n=1103). Taken together, our findings show that basal testosterone is not associated with having a leadership position in the corporate world or related to leadership styles in leaders. We suggest that basal testosterone could play a role in acquiring leadership positions through dominant and authoritarian behavior. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. Giant basal cell carcinoma of the eyelid: a case history | Fetohi | Pan ...

    African Journals Online (AJOL)

    Giant basal cell carcinoma of the eyelid: a case history. ... Abstract. Basal cell carcinoma is a type of skin cancer and rare, aggressive forms of basal cell ... She died 09 months after the end of irradiation in Intensive care unit due to septic shock.

  12. Stress during puberty boosts metabolic activation associated with fear-extinction learning in hippocampus, basal amygdala and cingulate cortex.

    Science.gov (United States)

    Toledo-Rodriguez, Maria; Pitiot, Alain; Paus, Tomáš; Sandi, Carmen

    2012-07-01

    Adolescence is characterized by major developmental changes that may render the individual vulnerable to stress and the development of psychopathologies in a sex-specific manner. Earlier we reported lower anxiety-like behavior and higher risk-taking and novelty seeking in rats previously exposed to peri-pubertal stress. Here we studied whether peri-pubertal stress affected the acquisition and extinction of fear memories and/or the associated functional engagement of various brain regions, as assessed with 2-deoxyglucose. We showed that while peri-pubertal stress reduced freezing during the acquisition of fear memories (training) in both sexes, it had a sex-specific effect on extinction of these memories. Moreover hippocampus, basal amygdala and cingulate and motor cortices showed higher metabolic rates during extinction in rats exposed to peri-pubertal stress. Interestingly, activation of the infralimbic cortex was negatively correlated with freezing during extinction only in control males, while only males stressed during puberty showed a significant correlation between behavior during extinction and metabolic activation of hippocampus, amygdala and paraventricular nucleus. No correlations between brain activation and behavior during extinction were observed in females (control or stress). These results indicate that exposure to peri-pubertal stress affects behavior and brain metabolism when the individual is exposed to an additional stressful challenge. Some of these effects are sex-specific. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. CT brain demonstration of basal ganglion calcification in adult HIV ...

    African Journals Online (AJOL)

    brain barrier has been postulated. Calcification of the basal ganglia in encephalopathic HIV/AIDS children has been relatively well documented. Only two adult HIV cases with basal ganglion calcification (BGC) have been reported in the literature.

  14. Orbitofacial Metastatic Basal Cell Carcinoma: Report of 10 Cases.

    Science.gov (United States)

    Branson, Sara V; McClintic, Elysa; Ozgur, Omar; Esmaeli, Bita; Yeatts, R Patrick

    To explore the clinical features, management, and prognosis of metastatic basal cell carcinoma originating in the orbitofacial region. Ten cases of orbitofacial metastatic basal cell carcinoma were identified by searching databases at 2 institutions from 1995 to 2015. A retrospective chart review was performed. Main outcome measures included patient demographics, lesion size, location of metastases, histologic subtype, recurrence rate, time between primary tumor diagnosis and metastasis, perineural invasion, treatment modalities, and survival from time of metastasis. The median tumor size at largest dimension was 3.3 cm (range, 1.9-11.5 cm), and 6 of 10 patients had at least 1 local recurrence before metastasis (range, 0-2 recurrences). The most common sites of metastasis included the ipsilateral parotid gland (n = 6) and cervical lymph nodes (n = 5). Histologic subtypes included infiltrative (n = 5), basosquamous (n = 2), nodular (n = 1), and mixed (n = 1). The median time from primary tumor diagnosis to metastasis was 7.5 years (range, 0-13). The median survival time from diagnosis of metastasis to last documented encounter or death was 5.3 years (range, 7 months-22.8 years). Treatment regimens included surgical excision, radiotherapy, and hedgehog inhibitors. Based on our findings, the following features may be markers of high risk orbitofacial basal cell carcinoma: 1) increasing tumor size, 2) local recurrence of the primary tumor, 3) aggressive histologic subtype, and 4) perineural invasion. Screening should include close observation of the primary site and tissues in the distribution of regional lymphatics, particularly the parotid gland and cervical lymph nodes.

  15. Nevoid Basal Cell Carcinoma Syndrome: A Case Report

    Directory of Open Access Journals (Sweden)

    Razavi

    2016-09-01

    Full Text Available Nevoid basal cell carcinoma syndrome (BCNS is an autosomal dominant inherited disorder. Multiple organ systems may be affected in this syndrome including abnormalities of the skin, skeletal system, genitourinary system and central nevus system. In this report, we present a case of Nevoid basal cell carcinoma syndrome in a 26-year-old male patient. The patient had multiple odontogenic keratocyst in the posterior of mandible, syndactyly in both hand and bifid rib. After enucleation and curettage, he was followed for two years. A number of both clinical and radiological criteria are used to diagnose this syndrome. Basal cell carcinoma syndrome is diagnosed with two major criteria or one major and two minor criteria. We must suspect this disorder in young patients with multiple odontogenic keratocyst and dental abnormalities whether related or not with other clinical manifestations or familial history.

  16. NF-κB activity in muscle from obese and type 2 diabetic subjects under basal and exercise-stimulated conditions.

    Science.gov (United States)

    Tantiwong, Puntip; Shanmugasundaram, Karthigayan; Monroy, Adriana; Ghosh, Sangeeta; Li, Mengyao; DeFronzo, Ralph A; Cersosimo, Eugenio; Sriwijitkamol, Apiradee; Mohan, Sumathy; Musi, Nicolas

    2010-11-01

    NF-κB is a transcription factor that controls the gene expression of several proinflammatory proteins. Cell culture and animal studies have implicated increased NF-κB activity in the pathogenesis of insulin resistance and muscle atrophy. However, it is unclear whether insulin-resistant human subjects have abnormal NF-κB activity in muscle. The effect that exercise has on NF-κB activity/signaling also is not clear. We measured NF-κB DNA-binding activity and the mRNA level of putative NF-κB-regulated myokines interleukin (IL)-6 and monocyte chemotactic protein-1 (MCP-1) in muscle samples from T2DM, obese, and lean subjects immediately before, during (40 min), and after (210 min) a bout of moderate-intensity cycle exercise. At baseline, NF-κB activity was elevated 2.1- and 2.7-fold in obese nondiabetic and T2DM subjects, respectively. NF-κB activity was increased significantly at 210 min following exercise in lean (1.9-fold) and obese (2.6-fold) subjects, but NF-κB activity did not change in T2DM. Exercise increased MCP-1 mRNA levels significantly in the three groups, whereas IL-6 gene expression increased significantly only in lean and obese subjects. MCP-1 and IL-6 gene expression peaked at the 40-min exercise time point. We conclude that insulin-resistant subjects have increased basal NF-κB activity in muscle. Acute exercise stimulates NF-κB in muscle from nondiabetic subjects. In T2DM subjects, exercise had no effect on NF-κB activity, which could be explained by the already elevated NF-κB activity at baseline. Exercise-induced MCP-1 and IL-6 gene expression precedes increases in NF-κB activity, suggesting that other factors promote gene expression of these cytokines during exercise.

  17. High-level expression, purification and characterization of a constitutively active thromboxane A2 receptor polymorphic variant.

    Directory of Open Access Journals (Sweden)

    Bing Xu

    Full Text Available G protein-coupled receptors (GPCRs exhibit some level of basal signaling even in the absence of a bound agonist. This basal or constitutive signaling can have important pathophysiological roles. In the past few years, a number of high resolution crystal structures of GPCRs have been reported, including two crystal structures of constitutively active mutants (CAM of the dim-light receptor, rhodopsin. The structural characterizations of CAMs are impeded by the lack of proper expression systems. The thromboxane A2 receptor (TP is a GPCR that mediates vasoconstriction and promotes thrombosis in response to the binding of thromboxane. Here, we report on the expression and purification of a genetic variant and CAM in TP, namely A160T, using tetracycline-inducible HEK293S-TetR and HEK293S (GnTI¯-TetR cell lines. Expression of the TP and the A160T genes in these mammalian cell lines resulted in a 4-fold increase in expression to a level of 15.8 ±0.3 pmol of receptor/mg of membrane protein. The receptors expressed in the HEK293S (GnTI(--TetR cell line showed homogeneous glycosylation. The functional yield of the receptors using a single step affinity purification was 45 µg/10⁶ cells. Temperature- dependent secondary structure changes of the purified TP and A160T receptors were characterized using circular dichroism (CD spectropolarimetry. The CD spectra shows that the loss of activity or thermal sensitivity that was previously observed for the A160T mutant, is not owing to large unfolding of the protein but rather to a more subtle effect. This is the first study to report on the successful high-level expression, purification, and biophysical characterization of a naturally occurring, diffusible ligand activated GPCR CAM.

  18. The relative phases of basal ganglia activities dynamically shape effective connectivity in Parkinson's disease.

    Science.gov (United States)

    Cagnan, Hayriye; Duff, Eugene Paul; Brown, Peter

    2015-06-01

    Optimal phase alignment between oscillatory neural circuits is hypothesized to optimize information flow and enhance system performance. This theory is known as communication-through-coherence. The basal ganglia motor circuit exhibits exaggerated oscillatory and coherent activity patterns in Parkinson's disease. Such activity patterns are linked to compromised motor system performance as evinced by bradykinesia, rigidity and tremor, suggesting that network function might actually deteriorate once a certain level of net synchrony is exceeded in the motor circuit. Here, we characterize the processes underscoring excessive synchronization and its termination. To this end, we analysed local field potential recordings from the subthalamic nucleus and globus pallidus of five patients with Parkinson's disease (four male and one female, aged 37-64 years). We observed that certain phase alignments between subthalamic nucleus and globus pallidus amplified local neural synchrony in the beta frequency band while others either suppressed it or did not induce any significant change with respect to surrogates. The increase in local beta synchrony directly correlated with how long the two nuclei locked to beta-amplifying phase alignments. Crucially, administration of the dopamine prodrug, levodopa, reduced the frequency and duration of periods during which subthalamic and pallidal populations were phase-locked to beta-amplifying alignments. Conversely ON dopamine, the total duration over which subthalamic and pallidal populations were aligned to phases that left beta-amplitude unchanged with respect to surrogates increased. Thus dopaminergic input shifted circuit dynamics from persistent periods of locking to amplifying phase alignments, associated with compromised motoric function, to more dynamic phase alignment and improved motoric function. This effect of dopamine on local circuit resonance suggests means by which novel electrical interventions might prevent resonance

  19. The expanding universe of disorders of the basal ganglia.

    Science.gov (United States)

    Obeso, Jose A; Rodriguez-Oroz, Maria C; Stamelou, Maria; Bhatia, Kailash P; Burn, David J

    2014-08-09

    The basal ganglia were originally thought to be associated purely with motor control. However, dysfunction and pathology of different regions and circuits are now known to give rise to many clinical manifestations beyond the association of basal ganglia dysfunction with movement disorders. Moreover, disorders that were thought to be caused by dysfunction of the basal ganglia only, such as Parkinson's disease and Huntington's disease, have diverse abnormalities distributed not only in the brain but also in the peripheral and autonomic nervous systems; this knowledge poses new questions and challenges. We discuss advances and the unanswered questions, and ways in which progress might be made. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Basal ganglia lesions in children and adults

    Energy Technology Data Exchange (ETDEWEB)

    Bekiesinska-Figatowska, Monika, E-mail: m.figatowska@mp.pl [Department of Diagnostic Imaging, Institute of Mother and Child, ul. Kasprzaka 17a, 01-211 Warsaw (Poland); Mierzewska, Hanna, E-mail: h.mierzewska@gmail.com [Department of Neurology of Children and Adolescents, Institute of Mother and Child, ul. Kasprzaka 17a, 01-211 Warsaw (Poland); Jurkiewicz, Elżbieta, E-mail: e-jurkiewicz@o2.pl [Department of Diagnostic Imaging, Children' s Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw (Poland)

    2013-05-15

    The term “basal ganglia” refers to caudate and lentiform nuclei, the latter composed of putamen and globus pallidus, substantia nigra and subthalamic nuclei and these deep gray matter structures belong to the extrapyramidal system. Many diseases may present as basal ganglia abnormalities. Magnetic resonance imaging (MRI) and computed tomography (CT) – to a lesser degree – allow for detection of basal ganglia injury. In many cases, MRI alone does not usually allow to establish diagnosis but together with the knowledge of age and circumstances of onset and clinical course of the disease is a powerful tool of differential diagnosis. The lesions may be unilateral: in Rassmussen encephalitis, diabetes with hemichorea/hemiballism and infarction or – more frequently – bilateral in many pathologic conditions. Restricted diffusion is attributable to infarction, acute hypoxic–ischemic injury, hypoglycemia, Leigh disease, encephalitis and CJD. Contrast enhancement may be seen in cases of infarction and encephalitis. T1-hyperintensity of the lesions is uncommon and may be observed unilaterally in case of hemichorea/hemiballism and bilaterally in acute asphyxia in term newborns, in hypoglycemia, NF1, Fahr disease and manganese intoxication. Decreased signal intensity on GRE/T2*-weighted images and/or SWI indicating iron, calcium or hemosiderin depositions is observed in panthotenate kinase-associated neurodegeneration, Parkinson variant of multiple system atrophy, Fahr disease (and other calcifications) as well as with the advancing age. There are a few papers in the literature reviewing basal ganglia lesions. The authors present a more detailed review with rich iconography from the own archive.

  1. Basal ganglia lesions in children and adults

    International Nuclear Information System (INIS)

    Bekiesinska-Figatowska, Monika; Mierzewska, Hanna; Jurkiewicz, Elżbieta

    2013-01-01

    The term “basal ganglia” refers to caudate and lentiform nuclei, the latter composed of putamen and globus pallidus, substantia nigra and subthalamic nuclei and these deep gray matter structures belong to the extrapyramidal system. Many diseases may present as basal ganglia abnormalities. Magnetic resonance imaging (MRI) and computed tomography (CT) – to a lesser degree – allow for detection of basal ganglia injury. In many cases, MRI alone does not usually allow to establish diagnosis but together with the knowledge of age and circumstances of onset and clinical course of the disease is a powerful tool of differential diagnosis. The lesions may be unilateral: in Rassmussen encephalitis, diabetes with hemichorea/hemiballism and infarction or – more frequently – bilateral in many pathologic conditions. Restricted diffusion is attributable to infarction, acute hypoxic–ischemic injury, hypoglycemia, Leigh disease, encephalitis and CJD. Contrast enhancement may be seen in cases of infarction and encephalitis. T1-hyperintensity of the lesions is uncommon and may be observed unilaterally in case of hemichorea/hemiballism and bilaterally in acute asphyxia in term newborns, in hypoglycemia, NF1, Fahr disease and manganese intoxication. Decreased signal intensity on GRE/T2*-weighted images and/or SWI indicating iron, calcium or hemosiderin depositions is observed in panthotenate kinase-associated neurodegeneration, Parkinson variant of multiple system atrophy, Fahr disease (and other calcifications) as well as with the advancing age. There are a few papers in the literature reviewing basal ganglia lesions. The authors present a more detailed review with rich iconography from the own archive

  2. Vitamin C improves basal metabolic rate and lipid profile in alloxan ...

    Indian Academy of Sciences (India)

    MADU

    3.1 Effect of vitamin C administration on basal metabolic rate. The basal metabolic rate values in diabetic rats and control are presented in figure 1. The basal metabolic rate (BMR) in diabetic rats was 1.19 ± 0.15 ml/h/g, while the BMR in control rats was 0.76 ± 0.89 ml/h/g. The BMR value in diabetic rats treated with vitamin ...

  3. Which features of advanced head and neck basal cell carcinoma are associated with perineural invasion?

    Directory of Open Access Journals (Sweden)

    André Bandiera de Oliveira Santos

    Full Text Available Abstract Introduction Perineural invasion is a unique route for tumor dissemination. In basal cell carcinomas, the incidence is low, but increases in advanced cases. Its importance is recognized but not fully understood. Objective To compare head and neck basal cell carcinomas with and without perineural invasion. Methods A retrospective medical chart review of multidisciplinary surgeries for basal cell carcinomas that required a head and neck surgery specialist in a tertiary referral center was performed. Clinical-demographics and histopathological features were analyzed. Results Of 354 cases, perineural invasion was present in 23.1%. Larger tumors and morpheaform subtype were statistically related to perineural invasion. Nodular and superficial subtypes were less frequent in positive cases. No significant difference was found in gender, age, ulceration, location, and mixed histology. Conclusion In this series of selected patients with basal cell carcinomas submitted to major resections, perineural invasion was clearly related to morpheaform subtype and to larger tumors. Other classically associated features, such as location in high-risk mask zone of the face, male gender and mixed histology, were not so strongly linked to perineural invasion.

  4. Zernike phase contrast cryo-electron tomography of sodium-driven flagellar hook-basal bodies from Vibrio alginolyticus.

    Science.gov (United States)

    Hosogi, Naoki; Shigematsu, Hideki; Terashima, Hiroyuki; Homma, Michio; Nagayama, Kuniaki

    2011-01-01

    Vibrio alginolyticus use flagella to swim. A flagellum consists of a filament, hook and basal body. The basal body is made up of a rod and several ring structures. This study investigates the structure of the T ring which is a unique component of the V. alginolyticus sodium ion-driven flagellar basal body. Using Zernike phase contrast (ZPC) cryo-electron tomography, we compared the 3D structures of purified hook-basal bodies (HBB) from a wild-type strain (KK148) and a deletion mutant lacking MotX and MotY (TH3), which are thought to form the T ring. ZPC images of HBBs had highly improved signal-to-noise ratio compared to conventional phase contrast images. We observed the outline of the HBBs from strains KK148 and TH3, and the TH3 mutant was missing its T ring. In the wild-type strain, the T ring was beneath the LP ring and seemed to form a ring shape with diameter of 32 nm. Copyright © 2010 Elsevier Inc. All rights reserved.

  5. Radiologic study of basal cell nevus syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Park, Tae Won [Dept. of Oral Radiology, College of Dentistry, Seoul National University, Seoul (Korea, Republic of)

    1988-11-15

    Several cases of jaw cyst-basal cell nevus-bifid rib syndrome are presented. This syndrome consists principally of multiple jaw cysts, basal cell nevi, and bifid ribs but no one component is present in all patients. The purpose of this paper is to review the multiple characteristics of this syndrome and present three cases in a family and additional 4 cases. The many malformations associated with the syndrome have variable expressively. In the cases, multiple jaw cysts, pal mar and plantar pittings, bridging of sella, temporoparietal bossing, hypertelorism, cleft palate, and dystopia canthoru m have been observed.

  6. Radiologic study of basal cell nevus syndrome

    International Nuclear Information System (INIS)

    Park, Tae Won

    1988-01-01

    Several cases of jaw cyst-basal cell nevus-bifid rib syndrome are presented. This syndrome consists principally of multiple jaw cysts, basal cell nevi, and bifid ribs but no one component is present in all patients. The purpose of this paper is to review the multiple characteristics of this syndrome and present three cases in a family and additional 4 cases. The many malformations associated with the syndrome have variable expressively. In the cases, multiple jaw cysts, pal mar and plantar pittings, bridging of sella, temporoparietal bossing, hypertelorism, cleft palate, and dystopia canthoru m have been observed.

  7. Heart rate responses induced by acoustic tempo and its interaction with basal heart rate.

    Science.gov (United States)

    Watanabe, Ken; Ooishi, Yuuki; Kashino, Makio

    2017-03-07

    Many studies have revealed the influences of music on the autonomic nervous system (ANS). Since previous studies focused on the effects of acoustic tempo on the ANS, and humans have their own physiological oscillations such as the heart rate (HR), the effects of acoustic tempo might depend on the HR. Here we show the relationship between HR elevation induced by acoustic tempo and individual basal HR. Since high tempo-induced HR elevation requires fast respiration, which is based on sympatho-respiratory coupling, we controlled the participants' respiration at a faster rate (20 CPM) than usual (15 CPM). We found that sound stimuli with a faster tempo than the individual basal HR increased the HR. However, the HR increased following a gradual increase in the acoustic tempo only when the extent of the gradual increase in tempo was within a specific range (around + 2%/min). The HR did not follow the increase in acoustic tempo when the rate of the increase in the acoustic tempo exceeded 3% per minute. These results suggest that the effect of the sympatho-respiratory coupling underlying the HR elevation caused by a high acoustic tempo depends on the basal HR, and the strength and the temporal dynamics of the tempo.

  8. Body Composition and Basal Metabolic Rate in Women with Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Marina de Figueiredo Ferreira

    2014-01-01

    Full Text Available Objective. The aim of this study was to determine which of the seven selected equations used to predict basal metabolic rate most accurately estimated the measured basal metabolic rate. Methods. Twenty-eight adult women with type 2 diabetes mellitus participated in this cross-sectional study. Anthropometric and biochemical variables were measured as well as body composition (by absorptiometry dual X-ray emission and basal metabolic rate (by indirect calorimetry; basal metabolic rate was also estimated by prediction equations. Results. There was a significant difference between the measured and the estimated basal metabolic rate determined by the FAO/WHO/UNU (Pvalue<0.021 and Huang et al. (Pvalue≤0.005 equations. Conclusion. The calculations using Owen et al’s. equation were the closest to the measured basal metabolic rate.

  9. High intensity aerobic exercise training improves chronic intermittent hypoxia-induced insulin resistance without basal autophagy modulation.

    Science.gov (United States)

    Pauly, Marion; Assense, Allan; Rondon, Aurélie; Thomas, Amandine; Dubouchaud, Hervé; Freyssenet, Damien; Benoit, Henri; Castells, Josiane; Flore, Patrice

    2017-03-03

    Chronic intermittent hypoxia (IH) associated with obstructive sleep apnea (OSA) is a major risk factor for cardiovascular and metabolic diseases (insulin resistance: IR). Autophagy is involved in the pathophysiology of IR and high intensity training (HIT) has recently emerged as a potential therapy. We aimed to confirm IH-induced IR in a tissue-dependent way and to explore the preventive effect of HIT on IR-induced by IH. Thirty Swiss 129 male mice were randomly assigned to Normoxia (N), Intermittent Hypoxia (IH: 21-5% FiO 2 , 30 s cycle, 8 h/day) or IH associated with high intensity training (IH HIT). After 8 days of HIT (2*24 min, 50 to 90% of Maximal Aerobic Speed or MAS on a treadmill) mice underwent 14 days IH or N. We found that IH induced IR, characterized by a greater glycemia, an impaired insulin sensitivity and lower AKT phosphorylation in adipose tissue and liver. Nevertheless, MAS and AKT phosphorylation were greater in muscle after IH. IH associated with HIT induced better systemic insulin sensitivity and AKT phosphorylation in liver. Autophagy markers were not altered in both conditions. These findings suggest that HIT could represent a preventive strategy to limit IH-induced IR without change of basal autophagy.

  10. Greenland deep boreholes inform on sliding and deformation of the basal ice

    Science.gov (United States)

    Dahl-Jensen, D.

    2017-12-01

    Repeated measurements of the deformation of the deep boreholes on the Greenland ice sheet informs on the basal sliding, near basal deformation and in general on the horizontal velocity through the ice. Results of the logging of the boreholes at Dye3, GRIP, NGRIP, NEEM and Camp Century through the last 40 years by the Danish Ice and Climate group will be presented and discussed. The results on the flow will be compared with the information on ice properties, impurity load and bedrock entrained material from the deep ice cores and the radio echo sounding images near the drill sites.The results show that the basal movement often happens in an impurity rich zone above the bedrock while pure basal sliding is limited even in the presence of basal water and significant basal melt.Most of the deep ice core sites are located close to ice divides where the surface velocity is limited so significant basal sliding is not expected. Exceptions are the surface velocities at Camp Century and Dye 3, both being 13 m/yr.Finally, the ongoing deep drilling at EGRIP will shortly be presented where we are drilling in the center of the North East Greenland Ice Stream (NEGIS).

  11. Basal cortisol levels and metabolic syndrome: A systematic review and meta-analysis of observational studies.

    Science.gov (United States)

    Garcez, Anderson; Leite, Heloísa Marquardt; Weiderpass, Elisabete; Paniz, Vera Maria Vieira; Watte, Guilherme; Canuto, Raquel; Olinto, Maria Teresa Anselmo

    2018-05-17

    To perform a qualitative synthesis (systematic review) and quantitative analysis (meta-analysis) to summarize the evidence regarding the relationship between basal cortisol levels and metabolic syndrome (MetS) in adults. A systematic search was performed in the PubMed, Embase, and PsycINFO databases for observational studies on the association between basal cortisol levels and MetS. The quality of individual studies was assessed by the Newcastle-Ottawa score. A random effects model was used to report pooled quantitative results and the I 2 statistic was used to assess heterogeneity. Egger's and Begg's tests were used to evaluate publication bias. Twenty-six studies (19 cross-sectional and seven case-control) met the inclusion criteria for the systematic review. The majority was classified as having a low risk of bias and used established criteria for the diagnosis of MetS. Twenty-one studies provided data on basal cortisol levels as continuous values and were included in the meta-analysis; they comprised 35 analyses and 11,808 subjects. Pooled results showed no significant difference in basal cortisol levels between subjects with and without MetS (standardized mean difference [SMD] = 0.02, 95% confidence interval [CI]=-0.11 to 0.14). There was high heterogeneity between the studies when all comparisons were considered (I 2  = 83.1%;p meta-analysis of studies evaluating saliva samples showed no significantly lower basal cortisol levels among subjects with MetS (SMD=-0.18, 95% CI=-0.37 to 0.01), whereas those studies that evaluated serum samples (SMD = 0.11, 95% CI=-0.02 to 0.24) and urine samples (SMD = 0.73, 95% CI=-0.40 to 1.86) showed no significantly higher basal cortisol levels among subjects with MetS. In the subgroup and meta-regression analyses, a significant difference in basal cortisol levels was observed according to study design, population base, age, gender, cortisol level assessment method, and study quality. This systematic review

  12. High fat diet blunts the effects of leptin on ventilation and on carotid body activity.

    Science.gov (United States)

    Ribeiro, Maria J; Sacramento, Joana F; Gallego-Martin, Teresa; Olea, Elena; Melo, Bernardete F; Guarino, Maria P; Yubero, Sara; Obeso, Ana; Conde, Silvia V

    2017-12-22

    Leptin plays a role in the control of breathing, acting mainly on central nervous system; however, leptin receptors have been recently shown to be expressed in the carotid body (CB), and this finding suggests a physiological role for leptin in the regulation of CB function. Leptin increases minute ventilation in both basal and hypoxic conditions in rats. It increases the frequency of carotid sinus nerve discharge in basal conditions, as well as the release of adenosine from the CB. However, in a metabolic syndrome animal model, the effects of leptin in ventilatory control, carotid sinus nerve activity and adenosine release by the CB are blunted. Although leptin may be involved in triggering CB overactivation in initial stages of obesity and dysmetabolism, resistance to leptin signalling and blunting of responses develops in metabolic syndrome animal models. Leptin plays a role in the control of breathing, acting mainly on central nervous system structures. Leptin receptors are expressed in the carotid body (CB) and this finding has been associated with a putative physiological role of leptin in the regulation of CB function. Since, the CBs are implicated in energy metabolism, here we tested the effects of different concentrations of leptin administration on ventilatory parameters and on carotid sinus nerve (CSN) activity in control and high-fat (HF) diet fed rats, in order to clarify the role of leptin in ventilation control in metabolic disease states. We also investigated the expression of leptin receptors and the neurotransmitters involved in leptin signalling in the CBs. We found that in non-disease conditions, leptin increases minute ventilation in both basal and hypoxic conditions. However, in the HF model, the effect of leptin in ventilatory control is blunted. We also observed that HF rats display an increased frequency of CSN discharge in basal conditions that is not altered by leptin, in contrast to what is observed in control animals. Leptin did not

  13. Novel Hedgehog pathway targets against basal cell carcinoma

    International Nuclear Information System (INIS)

    Tang, Jean Y.; So, P.-L.; Epstein, Ervin H.

    2007-01-01

    The Hedgehog signaling pathway plays a key role in directing growth and patterning during embryonic development and is required in vertebrates for the normal development of many structures, including the neural tube, axial skeleton, skin, and hair. Aberrant activation of the Hedgehog (Hh) pathway in adult tissue is associated with the development of basal cell carcinoma (BCC), medulloblastoma, and a subset of pancreatic, gastrointestinal, and other cancers. This review will provide an overview of what is known about the mechanisms by which activation of Hedgehog signaling leads to the development of BCCs and will review two recent papers suggesting that agents that modulate sterol levels might influence the Hh pathway. Thus, sterols may be a new therapeutic target for the treatment of BCCs, and readily available agents such as statins (HMG-CoA reductase inhibitors) or vitamin D might be helpful in reducing BCC incidence

  14. TP53 supports basal-like differentiation of mammary epithelial cells by preventing translocation of deltaNp63 into nucleoli

    Science.gov (United States)

    Munne, Pauliina M.; Gu, Yuexi; Tumiati, Manuela; Gao, Ping; Koopal, Sonja; Uusivirta, Sanna; Sawicki, Janet; Wei, Gong-Hong; Kuznetsov, Sergey G.

    2014-04-01

    Multiple observations suggest a cell type-specific role for TP53 in mammary epithelia. We developed an in vitro assay, in which primary mouse mammary epithelial cells (mMECs) progressed from lumenal to basal-like phenotypes based on expression of Krt18 or ΔNp63, respectively. Such transition was markedly delayed in Trp53-/- mMECs suggesting that Trp53 is required for specification of the basal, but not lumenal cells. Evidence from human basal-like cell lines suggests that TP53 may support the activity of ΔNp63 by preventing its translocation from nucleoplasm into nucleoli. In human lumenal cells, activation of TP53 by inhibiting MDM2 or BRCA1 restored the nucleoplasmic expression of ΔNp63. Trp53-/- mMECs eventually lost epithelial features resulting in upregulation of MDM2 and translocation of ΔNp63 into nucleoli. We propose that TP63 may contribute to TP53-mediated oncogenic transformation of epithelial cells and shed light on tissue- and cell type-specific biases observed for TP53-related cancers.

  15. Basal cell carcinoma preferentially arises from stem cells within hair follicle and mechanosensory niches.

    Science.gov (United States)

    Peterson, Shelby C; Eberl, Markus; Vagnozzi, Alicia N; Belkadi, Abdelmadjid; Veniaminova, Natalia A; Verhaegen, Monique E; Bichakjian, Christopher K; Ward, Nicole L; Dlugosz, Andrzej A; Wong, Sunny Y

    2015-04-02

    Basal cell carcinoma (BCC) is characterized by frequent loss of PTCH1, leading to constitutive activation of the Hedgehog pathway. Although the requirement for Hedgehog in BCC is well established, the identity of disease-initiating cells and the compartments in which they reside remain controversial. By using several inducible Cre drivers to delete Ptch1 in different cell compartments in mice, we show here that multiple hair follicle stem cell populations readily develop BCC-like tumors. In contrast, stem cells within the interfollicular epidermis do not efficiently form tumors. Notably, we observed that innervated Gli1-expressing progenitors within mechanosensory touch dome epithelia are highly tumorigenic. Sensory nerves activate Hedgehog signaling in normal touch domes, while denervation attenuates touch dome-derived tumors. Together, our studies identify varying tumor susceptibilities among different stem cell populations in the skin, highlight touch dome epithelia as "hot spots" for tumor formation, and implicate cutaneous nerves as mediators of tumorigenesis. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Cloned Bacillus subtilis alkaline protease (aprA) gene showing high level of keratinolytic activity.

    Science.gov (United States)

    Zaghloul, T I

    1998-01-01

    The Bacillus subtilis alkaline protease(aprA) gene was previously cloned on a pUBHO-derivative plasmid. High levels of expression and gene stability were demonstrated when B. subtilis cells were grown on the laboratory medium 2XSG. B. subtilis cells harboring the multicopy aprA gene were grown on basal medium, supplemented with 1 % chicken feather as a source of energy, carbon, and nitrogen. Proteolytic and keratinolytic activities were monitored throughout the cultivation time. A high level of keratinolytic activity was obtained, and this indicates that alkaline protease is acting as a keratinase. Furthermore, considerable amounts of soluble proteins and free amino acids were obtained as a result of the enzymatic hydrolysis of feather. Biodegradation of feather waste using these cells represents an alternative way to improve the nutritional value of feather, since feather waste is currently utilized on a limited basis as a dietary protein supplement for animal feedstuffs. Moreover, the release of free amino acids from feather and the secreted keratinase enzyme would promote industries based on feather waste.

  17. Mechanisms of basal ice formation in polar glaciers: An evaluation of the apron entrainment model

    Science.gov (United States)

    Fitzsimons, Sean; Webb, Nicola; Mager, Sarah; MacDonell, Shelley; Lorrain, Regi; Samyn, Denis

    2008-06-01

    Previous studies of polar glaciers have argued that basal ice can form when these glaciers override and entrain ice marginal aprons that accumulate adjacent to steep ice cliffs. To test this idea, we have studied the morphology, structure, composition, and deformation of the apron and basal ice at the terminus of Victoria Upper Glacier in the McMurdo dry valleys, which are located on the western coast of the Ross Sea at 77°S in southern Victoria Land, Antarctica. Our results show that the apron has two structural elements: an inner element that consists of strongly foliated ice that has a steep up-glacier dip, and an outer element that lacks a consistent foliation and has a down-glacier, slope-parallel dip. Although strain measurements show that the entire apron is deforming, the inner element is characterized by high strain rates, whereas relatively low rates of strain characterize the outer part of the apron. Co-isotopic analyses of the ice, together with analysis of solute chemistry and sedimentary characteristics, show that the apron is compositionally different from the basal ice. Our observations show that aprons may become deformed and partially entrained by advancing glaciers. However, such an ice marginal process does not provide a satisfactory explanation for the origin of basal ice observed at the ice margin. Our interpretation of the origin of basal ice is that it is formed by subglacial processes, which are likely to include deformation and entrainment of subglacial permafrost.

  18. Responses of dietary ileal amino acid digestibility to consumption of different cultivars of potatoes and conventional fibers in grower pigs fed a high-fat basal diet.

    Science.gov (United States)

    Wang, Q; Yang, X; Leonard, S; Archbold, T; Sullivan, J A; Duncan, A M; Ma, W D L; Bizimungu, B; Murphy, A; Htoo, J K; Fan, M Z

    2012-12-01

    Whereas dietary fibers are well recognized for nutritional management of human health issues, fiber is also known to be one of the dietary factors potentially affecting digestive use of dietary proteins. As a staple food, potato (Solanum tuberosum) may be a significant dietary fiber source. The objective of this study was to examine effects of dietary supplementation of six potato cultivar-genotype samples that differ in soluble fiber content and two conventional fiber components (i.e., cellulose and guar gum) on the apparent ileal AA digestibility in pigs fed a high-fat basal diet. The basal diet was formulated as a zero-fiber negative control (NC) to contain 41.5% poultry meal, 4% casein, 15% animal fat-oil blend, 2.8% sucrose, 31% corn (Zea mays) starch, 0.50% salt, and 0.40% trace mineral-vitamin supplement with fat contributing to 47% of the dietary GE. The two fiber diets were formulated by respectively diluting the basal diet with 10% guar gum and 10% cellulose at the expense of corn starch. Six other test diets were formulated by including 8.5% guar gum and further diluting the basal diet with 25.1% one of the six cultivar-genotype samples of dehydrated potato tuber powder to contain about 10% total dietary fiber at the expense of corn starch. Eighty-one 25-kg barrows were fitted with a simple T-cannula at the distal ileum and fed the diets according to a completely randomized block design with each block lasting 28 d. Compared with the NC, the ileal digestibility of Ala, Gly, and Pro were decreased (P guar gum whereas the digestibility of Gly was reduced (P guar gum compared with the NC. Our results suggest that dietary inclusion of fiber at 10% from guar gum and cellulose and contributed by potatoes may adversely affect digestive use of dietary protein.

  19. Altered neuronal firing pattern of the basal ganglia nucleus plays a role in levodopa-induced dyskinesia in patients with Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Xiaoyu eLi

    2015-11-01

    Full Text Available Background: Levodopa therapy alleviates the symptoms of Parkinson's disease (PD, but long-term treatment often leads to motor complications such as levodopa-induced dyskinesia (LID. Aim: To explore the neuronal activity in the basal ganglia nuclei in patients with PD and LID. Methods: Thirty patients with idiopathic PD (age, 55.1±11.0 years; disease duration, 8.7±5.6 years were enrolled between August 2006 and August 2013 at the Xuanwu Hospital, Capital Medical University, China. Their Hoehn and Yahr scores ranged from 2 to 4 and their UPDRS III scores were 28.5±5.2. Fifteen of them had severe LID (UPDRS IV scores of 6.7±1.6. Microelectrode recording was performed in the globus pallidus internus (GPi and subthalamic nucleus (STN during pallidotomy (n=12 or STN deep brain stimulation (DBS; bilateral, n=12; unilateral, n=6. The firing patterns and frequencies of various cell types were analyzed by assessing single cell interspike intervals (ISIs and the corresponding coefficient of variation (CV. Results: A total of 295 neurons were identified from the GPi (n=12 and STN (n=18. These included 26 (8.8% highly grouped discharge, 30 (10.2% low frequency firing, 78 (26.4% rapid tonic discharge, 103 (34.9% irregular activity, and 58 (19.7% tremor-related activity. There were significant differences between the two groups (P<0.05 for neurons with irregular firing, highly irregular cluster-like firing, and low-frequency firing. Conclusion: Altered neuronal activity was observed in the basal ganglia nucleus of GPi and STN, and may play important roles in the pathophysiology of PD and LID.

  20. A Case of Nonhealing Leg Ulcer: Basal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Didem Didar Balcı

    2008-06-01

    Full Text Available A 75-year-old woman was admitted to our outpatient clinic with a three-year history of a painless, nonhealing ulcer located on the left lower leg. She had no response to previous therapy with local wound care. Skin examination revealed an ulcer 2.7 x 3.7 cm in size, and the surrounding skin showed minimal erythema. The surface of the ulcer demonstrated shiny granulation tissue. Biopsy of the ulcer edge and base showed basal cell carcinoma. Venous Doppler ultrasonography and dermatological examination did not reveal chronic venous insufficiency. Basal cell carcinomas rarely arise from previous long-term ulcers or developing de novo. We suggest that patients who develop non-healing leg ulcers, should be examined for basal cell carcinoma.

  1. Basal Cell Carcinomas in Gorlin Syndrome: A Review of 202 Patients

    International Nuclear Information System (INIS)

    Jones, E. A.; Shenton, A.; Evans, D. G.; Sajid, M. I.

    2011-01-01

    Gorlin syndrome (Naevoid Basal Cell Carcinoma Syndrome) is a rare autosomal dominant syndrome caused by mutations in the PTCH gene with a birth incidence of approximately 1 in 19,000. Patients develop multiple basal cell carcinomas of the skin frequently in early life and also have a predisposition to additional malignancies such as medulloblastoma. Gorlin Syndrome patients also have developmental defects such as bifid ribs and other complications such as jaw keratocysts. We studied the incidence and frequency of basal cell carcinomas in 202 Gorlin syndrome patients from 62 families and compared this to their gender and mutation type. Our data suggests that the incidence of basal cell carcinomas is equal between males and females and the mutation type cannot be used to predict disease burden

  2. Network effects of subthalamic deep brain stimulation drive a unique mixture of responses in basal ganglia output

    OpenAIRE

    Humphries, Mark D.; Gurney, Kevin

    2012-01-01

    Deep brain stimulation (DBS) is a remarkably successful treatment for the motor symptoms of Parkinson's disease. High-frequency stimulation of the subthalamic nucleus (STN) within the basal ganglia is a main clinical target, but the physiological mechanisms of therapeutic STN DBS at the cellular and network level are unclear. We set out to begin to address the hypothesis that a mixture of responses in the basal ganglia output nuclei, combining regularized firing and inhibition, is a key contr...

  3. Body Composition and Basal Metabolic Rate in Women with Type 2 Diabetes Mellitus

    OpenAIRE

    de Figueiredo Ferreira, Marina; Detrano, Filipe; Coelho, Gabriela Morgado de Oliveira; Barros, Maria Elisa; Serrão Lanzillotti, Regina; Firmino Nogueira Neto, José; Portella, Emilson Souza; Serrão Lanzillotti, Haydée; Soares, Eliane de Abreu

    2014-01-01

    Objective. The aim of this study was to determine which of the seven selected equations used to predict basal metabolic rate most accurately estimated the measured basal metabolic rate. Methods. Twenty-eight adult women with type 2 diabetes mellitus participated in this cross-sectional study. Anthropometric and biochemical variables were measured as well as body composition (by absorptiometry dual X-ray emission) and basal metabolic rate (by indirect calorimetry); basal metabolic rate was als...

  4. Mice divergently selected for high and low basal metabolic rates evolved different cell size and organ mass.

    Science.gov (United States)

    Maciak, S; Bonda-Ostaszewska, E; Czarnołęski, M; Konarzewski, M; Kozłowski, J

    2014-03-01

    Evolution of metabolic rates of multicellular organisms is hypothesized to reflect the evolution of their cell architecture. This is likely to stem from a tight link between the sizes of cells and nuclei, which are expected to be inversely related to cell metabolism. Here, we analysed basal metabolic rate (BMR), internal organ masses and the cell/nucleus size in different tissues of laboratory mice divergently selected for high/low mass-corrected BMR and four random-bred mouse lines. Random-bred lines had intermediate levels of BMR as compared to low- and high-BMR lines. Yet, this pattern was only partly consistent with the between-line differences in cell/nucleus sizes. Erythrocytes and skin epithelium cells were smaller in the high-BMR line than in other lines, but the cells of low-BMR and random-bred mice were similar in size. On the other hand, the size of hepatocytes, kidney proximal tubule cells and duodenum enterocytes were larger in high-BMR mice than other lines. All cell and nucleus sizes were positively correlated, which supports the role of the nucleus in cell size regulation. Our results suggest that the evolution of high BMR involves a reduction in cell size in specialized tissues, whose functions are primarily dictated by surface-to-volume ratios, such as erythrocytes. High BMR may, however, also incur an increase in cell size in tissues with an intense transcription and translation, such as hepatocytes. © 2014 The Authors. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

  5. Deep brain stimulation changes basal ganglia output nuclei firing pattern in the dystonic hamster.

    Science.gov (United States)

    Leblois, Arthur; Reese, René; Labarre, David; Hamann, Melanie; Richter, Angelika; Boraud, Thomas; Meissner, Wassilios G

    2010-05-01

    Dystonia is a heterogeneous syndrome of movement disorders characterized by involuntary muscle contractions leading to abnormal movements and postures. While medical treatment is often ineffective, deep brain stimulation (DBS) of the internal pallidum improves dystonia. Here, we studied the impact of DBS in the entopeduncular nucleus (EP), the rodent equivalent of the human globus pallidus internus, on basal ganglia output in the dt(sz)-hamster, a well-characterized model of dystonia by extracellular recordings. Previous work has shown that EP-DBS improves dystonic symptoms in dt(sz)-hamsters. We report that EP-DBS changes firing pattern in the EP, most neurons switching to a less regular firing pattern during DBS. In contrast, EP-DBS did not change the average firing rate of EP neurons. EP neurons display multiphasic responses to each stimulation impulse, likely underlying the disruption of their firing rhythm. Finally, neurons in the substantia nigra pars reticulata display similar responses to EP-DBS, supporting the idea that EP-DBS affects basal ganglia output activity through the activation of common afferent fibers. Copyright 2010 Elsevier Inc. All rights reserved.

  6. Basal ganglia calcification on computed tomography in systemic lupus erythematosus

    International Nuclear Information System (INIS)

    Nagaoka, Shohei; Tani, Kenji; Ishigatsubo, Yoshiaki

    1988-01-01

    The development of basal ganglia calcification was studied in 85 patients with systemic lupus erythematosus (SLE) by computed tomography (CT). Bilateral calcification of the basal ganglia was found to occur in 5 patients (5.9 %) with SLE, but was not seen in patients with rheumatoid arthritis and progressive systemic sclerosis. All were female with a mean age of 42 years (range 29 - 49). The patients with calcification of the basal ganglia had neurological symptoms, such as psychiatric problems (3 cases), grand mal seizures (1 case), CSF abnormalities (2 cases), and EEG changes (4 cases). There were significantly higher incidences of alopecia, cutaneous vasculitis, leukopenia, and thrombocytopenia in the group with calcifications than those in the group with normal CT findings. Circulating immune complexes were detected and LE tests were positive in 2 patients. Endocrinological examination showed no abnormality in any. We suggest that basal ganglia calcification in SLE might be related to cerebral vasculitis. (author)

  7. Basal ganglia calcification on computed tomography in systemic lupus erythematosus

    Energy Technology Data Exchange (ETDEWEB)

    Nagaoka, Shohei; Tani, Kenji; Ishigatsubo, Yoshiaki and others

    1988-09-01

    The development of basal ganglia calcification was studied in 85 patients with systemic lupus erythematosus (SLE) by computed tomography (CT). Bilateral calcification of the basal ganglia was found to occur in 5 patients (5.9 %) with SLE, but was not seen in patients with rheumatoid arthritis and progressive systemic sclerosis. All were female with a mean age of 42 years (range 29 - 49). The patients with calcification of the basal ganglia had neurological symptoms, such as psychiatric problems (3 cases), grand mal seizures (1 case), CSF abnormalities (2 cases), and EEG changes (4 cases). There were significantly higher incidences of alopecia, cutaneous vasculitis, leukopenia, and thrombocytopenia in the group with calcifications than those in the group with normal CT findings. Circulating immune complexes were detected and LE tests were positive in 2 patients. Endocrinological examination showed no abnormality in any. We suggest that basal ganglia calcification in SLE might be related to cerebral vasculitis.

  8. Basal cell nevus syndrome: 2 case reports

    International Nuclear Information System (INIS)

    Kim, Jae Duk; Seo, Yo Seob; Kim, Jin Soo

    2008-01-01

    The basal cell nevus syndrome (BCNS) is an autosomal dominant disorder, characterized by basal cell carcinomas, odontogenic keratocysts and skeletal abnormalities. We experienced two cases that represented several characteristics of BCNS. Case 1: a thirty three year-old man visited CSU hospital. His radiographs showed four cystic lesions at both maxillary sinus and both mandibular angle, with bifid rib and ectopic calcification of falx cerebri. After marsupialization and enucleation, recurrent and newly developing tendency were found on his follow-up radiographs. Case 2: a seventeen year-old man had four large cystic lesions which were diagnosed as odontogenic keratocysts. He had craniofacial anomalies which included ectopic calcification and frontal bossing.

  9. Basal Ganglia Calcification with Tetanic Seizure Suggest Mitochondrial Disorder

    OpenAIRE

    Finsterer, Josef; Enzelsberger, Barbara; Bastowansky, Adam

    2017-01-01

    Patient: Female, 65 Final Diagnosis: Mitochondrial disorder Symptoms: Headache ? tetanic seizure Medication: Diazepam Clinical Procedure: Admission Specialty: Neurology Objective: Challenging differential diagnosis Background: Basal ganglia calcification (BGC) is a rare sporadic or hereditary central nervous system (CNS) abnormality, characterized by symmetric or asymmetric calcification of the basal ganglia. Case Report: We report the case of a 65-year-old Gypsy female who was admitted for a...

  10. Concentrated insulins: the new basal insulins

    Directory of Open Access Journals (Sweden)

    Lamos EM

    2016-03-01

    Full Text Available Elizabeth M Lamos,1 Lisa M Younk,2 Stephen N Davis3 1Division of Endocrinology, Diabetes and Nutrition, 2Department of Medicine, University of Maryland School of Medicine, 3Department of Medicine, University of Maryland Medical Center, Baltimore, MD, USA Introduction: Insulin therapy plays a critical role in the treatment of type 1 and type 2 diabetes mellitus. However, there is still a need to find basal insulins with 24-hour coverage and reduced risk of hypoglycemia. Additionally, with increasing obesity and insulin resistance, the ability to provide clinically necessary high doses of insulin at low volume is also needed. Areas covered: This review highlights the published reports of the pharmacokinetic (PK and glucodynamic properties of concentrated insulins: Humulin-R U500, insulin degludec U200, and insulin glargine U300, describes the clinical efficacy, risk of hypoglycemic, and metabolic changes observed, and finally, discusses observations about the complexity of introducing a new generation of concentrated insulins to the therapeutic market. Conclusion: Humulin-R U500 has a similar onset but longer duration of action compared with U100 regular insulin. Insulin glargine U300 has differential PK/pharmacodynamic effects when compared with insulin glargine U100. In noninferiority studies, glycemic control with degludec U200 and glargine U300 is similar to insulin glargine U100 and nocturnal hypoglycemia is reduced. Concentrated formulations appear to behave as separate molecular entities when compared with earlier U100 insulin analog compounds. In the review of available published data, newer concentrated basal insulins may offer an advantage in terms of reduced intraindividual variability as well as reducing the injection burden in individuals requiring high-dose and large volume insulin therapy. Understanding the PK and pharmacodynamic properties of this new generation of insulins is critical to safe dosing, dispensing, and administration

  11. Is basal ultrasensitive measurement of calcitonin capable of substituting for the pentagastrin-stimulation test?

    Science.gov (United States)

    Pina, Géraldine; Dubois, Séverine; Murat, Arnaud; Berger, Nicole; Niccoli, Patricia; Peix, Jean-Louis; Cohen, Régis; Guillausseau, Claudine; Charrie, Anne; Chabre, Olivier; Cornu, Catherine; Borson-Chazot, Françoise; Rohmer, Vincent

    2013-03-01

    To evaluate a second-generation assay for basal serum calcitonin (CT) measurements compared with the pentagastrin-stimulation test for the diagnosis of inherited medullary thyroid carcinoma (MTC) and the follow-up of patients with MTC after surgery. Recent American Thyroid Association recommendations suggest the use of basal CT alone to diagnose and assess follow-up of MTC as the pentagastrin (Pg) test is unavailable in many countries. Multicentric prospective study. A total of 162 patients with basal CT basal and Pg-stimulated CT measurements using a second-generation assay with 5-ng/l functional sensitivity. Ninety-five per cent of patients with basal CT ≥ 5 ng/l and 25% of patients with basal CT stimulation test (Pg CT >10 ng/l). Compared with the reference Pg test, basal CT ≥ 5 ng/l had 99% specificity, a 95%-positive predictive value but only 35% sensitivity (P basal CT instead of the previously used 10-ng/l threshold. The ultrasensitive CT assay reduces the false-negative rate of basal CT measurements when diagnosing familial MTC and in postoperative follow-up compared with previously used assays. However, its sensitivity to detect C-cell disease remains lower than that of the Pg-stimulation test. © 2012 Blackwell Publishing Ltd.

  12. Requirement of ERα and basal activities of EGFR and Src kinase in Cd-induced activation of MAPK/ERK pathway in human breast cancer MCF-7 cells

    Energy Technology Data Exchange (ETDEWEB)

    Song, Xiulong, E-mail: songxiulong@hotmail.com; Wei, Zhengxi; Shaikh, Zahir A., E-mail: zshaikh@uri.edu

    2015-08-15

    Cadmium (Cd) is a common environmental toxicant and an established carcinogen. Epidemiological studies implicate Cd with human breast cancer. Low micromolar concentrations of Cd promote proliferation of human breast cancer cells in vitro. The growth promotion of breast cancer cells is associated with the activation of MAPK/ERK pathway. This study explores the mechanism of Cd-induced activation of MAPK/ERK pathway. Specifically, the role of cell surface receptors ERα, EGFR, and Src kinase was evaluated in human breast cancer MCF-7 cells treated with 1–3 μM Cd. The activation of ERK was studied using a serum response element (SRE) luciferase reporter assay. Receptor phosphorylation was detected by Western blot analyses. Cd treatment increased both the SRE reporter activity and ERK1/2 phosphorylation in a concentration-dependent manner. Cd treatment had no effect on reactive oxygen species (ROS) generation. Also, blocking the entry of Cd into the cells with manganese did not diminish Cd-induced activation of MAPK/ERK. These results suggest that the effect of Cd was likely not caused by intracellular ROS generation, but through interaction with the membrane receptors. While Cd did not appear to activate either EGFR or Src kinase, their inhibition completely blocked the Cd-induced activation of ERK as well as cell proliferation. Similarly, silencing ERα with siRNA or use of ERα antagonist blocked the effects of Cd. Based on these results, it is concluded that not only ERα, but also basal activities of EGFR and Src kinase are essential for Cd-induced signal transduction and activation of MAPK/ERK pathway for breast cancer cell proliferation. - Highlights: • Low micromolar concentrations of Cd rapidly activate ERK1/2 in MCF-7 cells. • Signal transduction and resulting cell proliferation require EGFR, ERα, and Src. • These findings implicate Cd in promotion of breast cancer.

  13. Priming stimulation of basal but not lateral amygdala affects long-term potentiation in the rat dentate gyrus in vivo.

    Science.gov (United States)

    Li, Z; Richter-Levin, G

    2013-08-29

    The amygdaloid complex, or amygdala, has been implicated in assigning emotional significance to sensory information and producing appropriate behavioral responses to external stimuli. The lateral and basal nuclei (lateral and basal amygdala), which are termed together as basolateral amygdala, play a critical role in emotional and motivational learning and memory. It has been established that the basolateral amygdala activation by behavioral manipulations or direct electrical stimulation can modulate hippocampal long-term potentiation (LTP), a putative cellular mechanism of memory. However, the specific functional role of each subnucleus in the modulation of hippocampal LTP has not been studied yet, even though studies have shown cytoarchitectural differences between the basal and lateral amygdala and differences in the connections of each one of them to other brain areas. In this study we have tested the effects of lateral or basal amygdala pre-stimulation on hippocampal dentate gyrus LTP, induced by theta burst stimulation of the perforant path, in anesthetized rats. We found that while priming stimulation of the lateral amygdala did not affect LTP of the dentate gyrus, priming stimulation of the basal amygdala enhanced the LTP response when the priming stimulation was relatively weak, but impaired it when it was relatively strong. These results show that the basal and lateral nuclei of the amygdala, which have been already shown to differ in their anatomy and connectivity, may also have different functional roles. These findings raise the possibility that the lateral and basal amygdala differentially modulate memory processes in the hippocampus under emotional and motivational situations. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  14. Basal Cell Carcinomas in Gorlin Syndrome: A Review of 202 Patients

    Directory of Open Access Journals (Sweden)

    Elizabeth A. Jones

    2011-01-01

    Full Text Available Gorlin syndrome (Naevoid Basal Cell Carcinoma Syndrome is a rare autosomal dominant syndrome caused by mutations in the PTCH gene with a birth incidence of approximately 1 in 19,000. Patients develop multiple basal cell carcinomas of the skin frequently in early life and also have a predisposition to additional malignancies such as medulloblastoma. Gorlin Syndrome patients also have developmental defects such as bifid ribs and other complications such as jaw keratocysts. We studied the incidence and frequency of basal cell carcinomas in 202 Gorlin syndrome patients from 62 families and compared this to their gender and mutation type. Our data suggests that the incidence of basal cell carcinomas is equal between males and females and the mutation type cannot be used to predict disease burden.

  15. Electrophysiological Evidences of Organization of Cortical Motor Information in the Basal Ganglia

    Directory of Open Access Journals (Sweden)

    Hirokazu Iwamuro

    2011-05-01

    Full Text Available During the last two decades, the many developments in the treatment of movement disorders such as Parkinson disease and dystonia have enhanced our understanding on organization of the basal ganglia, and this knowledge has led to other advances in the field. According to many electrophysiological and anatomical findings, it is considered that motor information from different cortical areas is processed through several cortico-basal ganglia loops principally in a parallel fashion and somatotopy from each cortical area is also well preserved in each loop. Moreover, recent studies suggest that not only the parallel processing but also some convergence of information occur through the basal ganglia. Information from cortical areas whose functions are close to each other tends to converge in the basal ganglia. The cortico-basal ganglia loops should be comprehended more as a network rather than as separated subdivisions. However, the functions of this convergence still remain unknown. It is important even for clinical doctors to be well informed about this kind of current knowledge because some symptoms of movement disorders may be explained by disorganization of the information network in the basal ganglia.

  16. Cyclin D2 in the basal process of neural progenitors is linked to non-equivalent cell fates

    Science.gov (United States)

    Tsunekawa, Yuji; Britto, Joanne M; Takahashi, Masanori; Polleux, Franck; Tan, Seong-Seng; Osumi, Noriko

    2012-01-01

    Asymmetric cell division plays an indispensable role during corticogenesis for producing new neurons while maintaining a self-renewing pool of apical progenitors. The cellular and molecular determinants favouring asymmetric division are not completely understood. Here, we identify a novel mechanism for generating cellular asymmetry through the active transportation and local translation of Cyclin D2 mRNA in the basal process. This process is regulated by a unique cis-regulatory sequence found in the 3′ untranslated region (3′UTR) of the mRNA. Unequal inheritance of Cyclin D2 protein to the basally positioned daughter cell with the basal process confers renewal of the apical progenitor after asymmetric division. Conversely, depletion of Cyclin D2 in the apically positioned daughter cell results in terminal neuronal differentiation. We demonstrate that Cyclin D2 is also expressed in the developing human cortex within similar domains, thus indicating that its role as a fate determinant is ancient and conserved. PMID:22395070

  17. Trichoepithelioma And Multiple Basal Cell Epithelioma

    Directory of Open Access Journals (Sweden)

    Dey S.K

    1996-01-01

    Full Text Available A combination of multiple trichoepithelioma and basal cell epithelioma is reported. Although malignant degeneration of trichoepithelioma is debated, clinical and histopathological studies, in our case, hint at that. The case is reported for its rarity.

  18. Idiopathic Basal Ganglia Calcification Presented with Impulse Control Disorder

    OpenAIRE

    Sahin, Cem; Levent, Mustafa; Akbaba, Gulhan; Kara, Bilge; Yeniceri, Emine Nese; Inanc, Betul Battaloglu

    2015-01-01

    Primary familial brain calcification (PFBC), also referred to as Idiopathic Basal Ganglia Calcification (IBGC) or “Fahr’s disease,” is a clinical condition characterized by symmetric and bilateral calcification of globus pallidus and also basal ganglions, cerebellar nuclei, and other deep cortical structures. It could be accompanied by parathyroid disorder and other metabolic disturbances. The clinical features are dysfunction of the calcified anatomic localization. IBGC most commonly present...

  19. Simulating the roles of crevasse routing of surface water and basal friction on the surge evolution of Basin 3, Austfonna ice cap

    Directory of Open Access Journals (Sweden)

    Y. Gong

    2018-05-01

    Full Text Available The marine-terminating outlet in Basin 3, Austfonna ice cap, has been accelerating since the mid-1990s. Stepwise multi-annual acceleration associated with seasonal summer speed-up events was observed before the outlet entered the basin-wide surge in autumn 2012. We used multiple numerical models to explore hydrologic activation mechanisms for the surge behaviour. A continuum ice dynamic model was used to invert basal friction coefficient distributions using the control method and observed surface velocity data between April 2012 and July 2014. This has provided input to a discrete element model capable of simulating individual crevasses, with the aim of finding locations where meltwater entered the glacier during the summer and reached the bed. The possible flow paths of surface meltwater reaching the glacier bed as well as those of meltwater produced at the bed were calculated according to the gradient of the hydraulic potential.The inverted friction coefficients show the unplugging of the stagnant ice front and expansion of low-friction regions before the surge reached its peak velocity in January 2013. Crevasse distribution reflects the basal friction pattern to a high degree. The meltwater reaches the bed through the crevasses located above the margins of the subglacial valley and the basal melt that is generated mainly by frictional heating flows either to the fast-flowing units or potentially accumulates in an overdeepened region. Based on these results, the mechanisms facilitated by basal meltwater production, crevasse opening and the routing of meltwater to the bed are discussed for the surge in Basin 3.

  20. Simulating the roles of crevasse routing of surface water and basal friction on the surge evolution of Basin 3, Austfonna ice cap

    Science.gov (United States)

    Gong, Yongmei; Zwinger, Thomas; Åström, Jan; Altena, Bas; Schellenberger, Thomas; Gladstone, Rupert; Moore, John C.

    2018-05-01

    The marine-terminating outlet in Basin 3, Austfonna ice cap, has been accelerating since the mid-1990s. Stepwise multi-annual acceleration associated with seasonal summer speed-up events was observed before the outlet entered the basin-wide surge in autumn 2012. We used multiple numerical models to explore hydrologic activation mechanisms for the surge behaviour. A continuum ice dynamic model was used to invert basal friction coefficient distributions using the control method and observed surface velocity data between April 2012 and July 2014. This has provided input to a discrete element model capable of simulating individual crevasses, with the aim of finding locations where meltwater entered the glacier during the summer and reached the bed. The possible flow paths of surface meltwater reaching the glacier bed as well as those of meltwater produced at the bed were calculated according to the gradient of the hydraulic potential. The inverted friction coefficients show the unplugging of the stagnant ice front and expansion of low-friction regions before the surge reached its peak velocity in January 2013. Crevasse distribution reflects the basal friction pattern to a high degree. The meltwater reaches the bed through the crevasses located above the margins of the subglacial valley and the basal melt that is generated mainly by frictional heating flows either to the fast-flowing units or potentially accumulates in an overdeepened region. Based on these results, the mechanisms facilitated by basal meltwater production, crevasse opening and the routing of meltwater to the bed are discussed for the surge in Basin 3.

  1. Basal Forebrain Cholinergic Deficits Reduce Glucose Metabolism and Function of Cholinergic and GABAergic Systems in the Cingulate Cortex.

    Science.gov (United States)

    Jeong, Da Un; Oh, Jin Hwan; Lee, Ji Eun; Lee, Jihyeon; Cho, Zang Hee; Chang, Jin Woo; Chang, Won Seok

    2016-01-01

    Reduced brain glucose metabolism and basal forebrain cholinergic neuron degeneration are common features of Alzheimer's disease and have been correlated with memory function. Although regions representing glucose hypometabolism in patients with Alzheimer's disease are targets of cholinergic basal forebrain neurons, the interaction between cholinergic denervation and glucose hypometabolism is still unclear. The aim of the present study was to evaluate glucose metabolism changes caused by cholinergic deficits. We lesioned basal forebrain cholinergic neurons in rats using 192 immunoglobulin G-saporin. After 3 weeks, lesioned animals underwent water maze testing or were analyzed by ¹⁸F-2-fluoro-2-deoxyglucose positron emission tomography. During water maze probe testing, performance of the lesioned group decreased with respect to time spent in the target quadrant and platform zone. Cingulate cortex glucose metabolism in the lesioned group decreased, compared with the normal group. Additionally, acetylcholinesterase activity and glutamate decarboxylase 65/67 expression declined in the cingulate cortex. Our results reveal that spatial memory impairment in animals with selective basal forebrain cholinergic neuron damage is associated with a functional decline in the GABAergic and cholinergic system associated with cingulate cortex glucose hypometabolism.

  2. Importance of constitutive activity and arrestin-independent mechanisms for intracellular trafficking of the ghrelin receptor

    DEFF Research Database (Denmark)

    Holliday, Nicholas D; Holst, Birgitte; Rodionova, Elena A

    2007-01-01

    . Furthermore the interaction between phosphorylated receptors and beta-arrestin adaptor proteins has been examined. Replacement of the FLAG-tagged GhrelinR C tail with the equivalent GPR39 domain (GhR-39 chimera) preserved G(q) signaling. However in contrast to the GhrelinR, GhR-39 receptors exhibited no basal......,9), Leu(11)] substance P and a naturally occurring mutant GhrelinR (A204E) with eliminated constitutive activity inhibited basal GhrelinR internalization. Surprisingly, we found that noninternalizing GPR39 was highly phosphorylated and that basal and agonist-induced phosphorylation of the GhR-39 chimera......, but the high levels of GPR39 phosphorylation, and of the GhR-39 chimera, are not sufficient to drive endocytosis. In addition, basal GhrelinR internalization occurs independently of beta-arrestins....

  3. An upstream activation element exerting differential transcriptional activation on an archaeal promoter

    DEFF Research Database (Denmark)

    Peng, Nan; Xia, Qiu; Chen, Zhengjun

    2009-01-01

    S gene encoding an arabinose binding protein was characterized using an Sulfolobus islandicus reporter gene system. The minimal active araS promoter (P(araS)) was found to be 59 nucleotides long and harboured four promoter elements: an ara-box, an upstream transcription factor B-responsive element (BRE......), a TATA-box and a proximal promoter element, each of which contained important nucleotides that either greatly decreased or completely abolished promoter activity upon mutagenesis. The basal araS promoter was virtually inactive due to intrinsically weak BRE element, and the upstream activating sequence...... (UAS) ara-box activated the basal promoter by recruiting transcription factor B to its BRE. While this UAS ensured a general expression from an inactive or weak basal promoter in the presence of other tested carbon resources, it exhibited a strong arabinose-responsive transcriptional activation. To our...

  4. Basal cell adenocarcinoma of minor salivary and seromucous glands of the head and neck region.

    Science.gov (United States)

    Fonseca, I; Soares, J

    1996-05-01

    Basal cell adenocarcinoma of salivary glands is an uncommon and recently described entity occurring almost exclusively at the major salivary glands. This report provides an overview of the clinicopathologic profile of this neoplasm by including the personal experience on the clinical features, microscopic and ultrastructural characteristics, proliferation activity, and DNA tumor patterns of 12 lesions occurring at the minor salivary glands of the head and neck region, where basal cell adenocarcinoma is probably an underecognized entity, previously reported under different designations. Basal cell adenocarcinoma predominates at the seventh decade without sex preference. The tumors affecting the minor salivary glands occur most frequently at the oral cavity (jugal mucosa, palate) and the upper respiratory tract. The prevalent histologic tumor pattern is represented by solid neoplastic aggregates with a peripheral cell palisading arrangement frequently delineated by basement membrane-like material. The neoplastic clusters are formed by two cell populations: the small dark cell type (that predominates) and a large cell type. Necrosis, either of the comedo or the apoptotic type, is a frequent finding. Perineural growth occurs in 50% of the cases and vascular permeation in 25%. Immunohistochemistry identifies a dual differentiation with a reactivity pattern indicative of ductal epithelial and myoepithelial differentiation, which can be confirmed by electron microscopy. The differential diagnosis of the neoplasm includes its benign counterpart, the basal cell adenoma, solid variant of adenoid cystic carcinoma, undifferentiated carcinoma, and basaloid squamous carcinoma. The tumors recur more frequently than lesions originating in major salivary glands. Mortality is associated with the anatomic site of the lesion, advanced stage, residual neoplasia at surgery, and tumor recurrence. The importance of recognizing basal cell adenocarcinoma outside major salivary glands is

  5. Identification of hamster inducible nitric oxide synthase (iNOS) promoter sequences that influence basal and inducible iNOS expression

    Science.gov (United States)

    Saldarriaga, Omar A.; Travi, Bruno L.; Choudhury, Goutam Ghosh; Melby, Peter C.

    2012-01-01

    IFN-γ/LPS-activated hamster (Mesocricetus auratus) macrophages express significantly less iNOS (NOS2) than activated mouse macrophages, which contributes to the hamster's susceptibility to intracellular pathogens. We determined a mechanism responsible for differences in iNOS promoter activity in hamsters and mice. The HtPP (1.2 kb) showed low basal and inducible promoter activity when compared with the mouse, and sequences within a 100-bp region (−233 to −133) of the mouse and hamster promoters influenced this activity. Moreover, within this 100 bp, we identified a smaller region (44 bp) in the mouse promoter, which recovered basal promoter activity when swapped into the hamster promoter. The mouse homolog (100-bp region) contained a cis-element for NF-IL-6 (−153/−142), which was absent in the hamster counterpart. EMSA and supershift assays revealed that the hamster sequence did not support the binding of NF-IL-6. Introduction of a functional NF-IL-6 binding sequence into the hamster promoter or its alteration in the mouse promoter revealed the critical importance of this transcription factor for full iNOS promoter activity. Furthermore, the binding of NF-IL-6 to the iNOS promoter (−153/−142) in vivo was increased in mouse cells but was reduced in hamster cells after IFN-γ/LPS stimulation. Differences in the activity of the iNOS promoters were evident in mouse and hamster cells, so they were not merely a result of species-specific differences in transcription factors. Thus, we have identified unique DNA sequences and a critical transcription factor, NF-IL-6, which contribute to the overall basal and inducible expression of hamster iNOS. PMID:22517919

  6. Nevoid basal cell carcinoma syndrome—case report and genetic study

    Directory of Open Access Journals (Sweden)

    Yu-Feng Huang

    2010-09-01

    Full Text Available Nevoid basal cell carcinoma syndrome (also named Gorlin-Goltz syndrome is a rare disease. Commonly seen features include multiple odontogenic keratocysts (OKCs, nevus-like basal cell carcinoma, and bifid ribs. Genetic alterations of the PTCH1 gene are associated with the disease. Herein, we report the case of a 15-year-old girl who presented with multiple OKCs, a bifid rib, ectopic calcification of the falx cer-ebri, and an arachnoid cyst of the cerebrum. No basal cell carcinoma was identified. In addition, a search for genetic alterations was performed on the patient. We identified a genetic mutation of C→T in exon 12 (c.1686 bp and a G→C mutation in intron 13 (g.91665 bp of the PTCH1 gene. Although a similar mutation in exon 12 was reported in a literature search, the mutation in intron 13 has not previously been reported. The patient has continued to be followed-up almost 3 years after the surgery with no recurrence of the OKCs or development of basal cell carcinoma.

  7. Dynamic thiol/disulphide homeostasis in patients with basal cell carcinoma.

    Science.gov (United States)

    Demirseren, Duriye Deniz; Cicek, Cagla; Alisik, Murat; Demirseren, Mustafa Erol; Aktaş, Akın; Erel, Ozcan

    2017-09-01

    The aim of this study is to measure and compare the dynamic thiol/disulphide homeostasis of patients with basal cell carcinoma and healthy subjects with a newly developed and original method. Thirty four patients attending our outpatient clinic and clinically and histopathologically diagnosed as nodular basal cell carcinoma, and age and gender matched 30 healthy individuals have been involved in the study. Thiol/disulphide homeostasis tests have been measured with a novel automatic spectrophotometric method developed and the results have been compared statistically. Serum native thiol and disulphide levels in the patient and control group show a considerable variance statistically (p = 0.028, 0.039, respectively). Total thiol levels do not reveal a considerable variation (p = 0.094). Disulphide/native thiol ratios and native thiol/total thiol ratios also show a considerable variance statistically (p = 0.012, 0.013, 0.010, respectively). Thiol disulphide homeostasis in patients with basal cell carcinoma alters in the way that disulphide gets lower and thiols get higher. Thiol/disulphide level is likely to have a role in basal cell carcinoma pathogenesis.

  8. Does basal metabolic rate predict weight gain?12

    Science.gov (United States)

    Anthanont, Pimjai; Jensen, Michael D

    2016-01-01

    Background: Some previous studies have indicated that a low basal metabolic rate (BMR) is an independent predictor of future weight gain, but low rates of follow-up and highly select populations may limit the ability to generalize the results. Objective: We assessed whether adults with a low BMR gain more weight than do adults with a high BMR who are living in a typical Western environment. Design: We extracted BMR, body-composition, demographic, and laboratory data from electronic databases of 757 volunteers who were participating in our research protocols at the Mayo Clinic between 1995 and 2012. Research study volunteers were always weight stable, had no acute illnesses and no confounding medication use, and were nonsmokers. The top and bottom 15th percentiles of BMR, adjusted for fat-free mass (FFM), fat mass, age, and sex, were identified. Follow-up electronic medical record system data were available for 163 subjects, which allowed us to determine their subsequent weight changes for ≥3 y (mean: ∼9.7 y). Results: By definition, the BMR was different in the high-BMR group (2001 ± 317 kcal/d; n = 86) than in the low-BMR group (1510 ± 222 kcal/d; n = 77), but they were comparable with respect to age, body mass index, FFM, and fat mass. Rates of weight gain were not greater in the bottom BMR group (0.3 ± 1.0 kg/y) than in the top BMR group (0.5 ± 1.5 kg/y) (P = 0.17). Conclusion: Adults with low BMRs did not gain more weight than did adults with high BMRs, implying that habitual differences in food intake or activity counterbalance variations in BMR as a risk factor for weight gain in a typical Western population. PMID:27581474

  9. Bilateral symmetrical basal ganglia and thalamic lesions in children: an update (2015)

    International Nuclear Information System (INIS)

    Zuccoli, Giulio; Yannes, Michael Paul; Nardone, Raffaele; Bailey, Ariel; Goldstein, Amy

    2015-01-01

    In children, many inherited or acquired neurological disorders may cause bilateral symmetrical signal intensity alterations in the basal ganglia and thalami. A literature review was aimed at assisting neuroradiologists, neurologists, infectious diseases specialists, and pediatricians to provide further understanding into the clinical and neuroimaging features in pediatric patients presenting with bilateral symmetrical basal ganglia and thalamic lesions on magnetic resonance imaging (MRI). We discuss hypoxic-ischemic, toxic, infectious, immune-mediated, mitochondrial, metabolic, and neurodegenerative disorders affecting the basal ganglia and thalami. Recognition and correct evaluation of basal ganglia abnormalities, together with a proper neurological examination and laboratory findings, may enable the identification of each of these clinical entities and lead to earlier diagnosis. (orig.)

  10. Bilateral symmetrical basal ganglia and thalamic lesions in children: an update (2015)

    Energy Technology Data Exchange (ETDEWEB)

    Zuccoli, Giulio [Children' s Hospital of Pittsburgh of UPMC, Section of Neuroradiology, Pittsburgh, PA (United States); Yannes, Michael Paul [University of Pittsburgh School of Medicine, Department of Radiology, Pittsburgh, PA (United States); Nardone, Raffaele [Paracelsus Medical University, Department of Neurology, Christian Doppler Klinik, Salzburg (Austria); Bailey, Ariel [West Virginia University, Department of Radiology, Morgantown, WV (United States); Goldstein, Amy [Children' s Hospital of Pittsburgh of UPMC, Department of Neurology, Section of Metabolic Disorders and Neurogenetics, Pittsburgh, PA (United States)

    2015-10-15

    In children, many inherited or acquired neurological disorders may cause bilateral symmetrical signal intensity alterations in the basal ganglia and thalami. A literature review was aimed at assisting neuroradiologists, neurologists, infectious diseases specialists, and pediatricians to provide further understanding into the clinical and neuroimaging features in pediatric patients presenting with bilateral symmetrical basal ganglia and thalamic lesions on magnetic resonance imaging (MRI). We discuss hypoxic-ischemic, toxic, infectious, immune-mediated, mitochondrial, metabolic, and neurodegenerative disorders affecting the basal ganglia and thalami. Recognition and correct evaluation of basal ganglia abnormalities, together with a proper neurological examination and laboratory findings, may enable the identification of each of these clinical entities and lead to earlier diagnosis. (orig.)

  11. Basal and Adrenocorticotropic Hormone Stimulated Plasma Cortisol Levels Among Egyptian Autistic Children: Relation to Disease Severity

    Directory of Open Access Journals (Sweden)

    Hewedi Doaa H

    2010-10-01

    Full Text Available Abstract Background Autism is a disorder of early childhood characterized by social impairment, communication abnormalities and stereotyped behaviors. The hypothalamic-pituitary-adrenocortical (HPA axis deserves special attention, since it is the basis for emotions and social interactions that are affected in autism. Aim To assess basal and stimulated plasma cortisol, and adrenocorticotropic hormone (ACTH levels in autistic children and their relationship to disease characteristics. Methods Fifty autistic children were studied in comparison to 50 healthy age-, sex- and pubertal stage- matched children. All subjects were subjected to clinical evaluation and measurement of plasma cortisol (basal and stimulated and ACTH. In addition, electroencephalography (EEG and intelligence quotient (IQ assessment were done for all autistic children. Results Sixteen% of autistic patients had high ACTH, 10% had low basal cortisol and 10% did not show adequate cortisol response to ACTH stimulation. Autistic patients had lower basal (p = 0.032 and stimulated cortisol (p = 0.04 and higher ACTH (p = 0.01 than controls. Childhood Autism Rating Scale (CARS score correlated positively with ACTH (r = 0.71, p = 0.02 and negatively with each of basal (r = -0.64, p = 0.04 and stimulated cortisol (r = -0.88, p Conclusions The observed hormonal changes may be due to a dysfunction in the HPA axis in autistic individuals. Further studies are warranted regarding the role of HPA axis dysfunction in the pathogenesis of autism.

  12. Shell bone histology indicates terrestrial palaeoecology of basal turtles

    OpenAIRE

    Scheyer, Torsten; Sander, P. Martin

    2009-01-01

    The palaeoecology of basal turtles from the Late Triassic was classically viewed as being semi-aquatic, similar to the lifestyle of modern snapping turtles. Lately, this view was questioned based on limb bone proportions, and a terrestrial palaeoecology was suggested for the turtle stem. Here, we present independent shell bone microstructural evidence for a terrestrial habitat of the oldest and basal most well-known turtles, i.e. the Upper Triassic Proterochersis robusta and Proganochelys que...

  13. A synthesis of the basal thermal state of the Greenland Ice Sheet

    Science.gov (United States)

    MacGregor, Joseph A; Fahnestock, Mark A; Catania, Ginny A; Aschwanden, Andy; Clow, Gary D.; Colgan, William T.; Gogineni, Prasad S.; Morlighem, Mathieu; Nowicki, Sophie M .J.; Paden, John D; Price, Stephen F.; Seroussi, Helene

    2016-01-01

    The basal thermal state of an ice sheet (frozen or thawed) is an important control upon its evolution, dynamics and response to external forcings. However, this state can only be observed directly within sparse boreholes or inferred conclusively from the presence of subglacial lakes. Here we synthesize spatially extensive inferences of the basal thermal state of the Greenland Ice Sheet to better constrain this state. Existing inferences include outputs from the eight thermomechanical ice-flow models included in the SeaRISE effort. New remote-sensing inferences of the basal thermal state are derived from Holocene radiostratigraphy, modern surface velocity and MODIS imagery. Both thermomechanical modeling and remote inferences generally agree that the Northeast Greenland Ice Stream and large portions of the southwestern ice-drainage systems are thawed at the bed, whereas the bed beneath the central ice divides, particularly their west-facing slopes, is frozen. Elsewhere, there is poor agreement regarding the basal thermal state. Both models and remote inferences rarely represent the borehole-observed basal thermal state accurately near NorthGRIP and DYE-3. This synthesis identifies a large portion of the Greenland Ice Sheet (about one third by area) where additional observations would most improve knowledge of its overall basal thermal state.

  14. A synthesis of the basal thermal state of the Greenland Ice Sheet.

    Science.gov (United States)

    MacGregor, Joseph A; Fahnestock, Mark A; Catania, Ginny A; Aschwanden, Andy; Clow, Gary D; Colgan, William T; Gogineni, S Prasad; Morlighem, Mathieu; Nowicki, Sophie M J; Paden, John D; Price, Stephen F; Seroussi, Hélène

    2016-08-10

    The basal thermal state of an ice sheet (frozen or thawed) is an important control upon its evolution, dynamics and response to external forcings. However, this state can only be observed directly within sparse boreholes or inferred conclusively from the presence of subglacial lakes. Here we synthesize spatially extensive inferences of the basal thermal state of the Greenland Ice Sheet to better constrain this state. Existing inferences include outputs from the eight thermomechanical ice-flow models included in the SeaRISE effort. New remote-sensing inferences of the basal thermal state are derived from Holocene radiostratigraphy, modern surface velocity and MODIS imagery. Both thermomechanical modeling and remote inferences generally agree that the Northeast Greenland Ice Stream and large portions of the southwestern ice-drainage systems are thawed at the bed, whereas the bed beneath the central ice divides, particularly their west-facing slopes, is frozen. Elsewhere, there is poor agreement regarding the basal thermal state. Both models and remote inferences rarely represent the borehole-observed basal thermal state accurately near NorthGRIP and DYE-3. This synthesis identifies a large portion of the Greenland Ice Sheet (about one third by area) where additional observations would most improve knowledge of its overall basal thermal state.

  15. Magellanic penguin telomeres do not shorten with age with increased reproductive effort, investment, and basal corticosterone.

    Science.gov (United States)

    Cerchiara, Jack A; Risques, Rosa Ana; Prunkard, Donna; Smith, Jeffrey R; Kane, Olivia J; Boersma, P Dee

    2017-08-01

    All species should invest in systems that enhance longevity; however, a fundamental adult life-history trade-off exists between the metabolic resources allocated to maintenance and those allocated to reproduction. Long-lived species will invest more in reproduction than in somatic maintenance as they age. We investigated this trade-off by analyzing correlations among telomere length, reproductive effort and output, and basal corticosterone in Magellanic penguins ( Spheniscus magellanicus ). Telomeres shorten with age in most species studied to date, and may affect adult survival. High basal corticosterone is indicative of stressful conditions. Corticosterone, and stress, has been linked to telomere shortening in other species. Magellanic penguins are a particularly good model organism for this question as they are an unusually long-lived species, exceeding their mass-adjusted predicted lifespan by 26%. Contrary to our hypothesis, we found adults aged 5 years to over 24 years of age had similar telomere lengths. Telomeres of adults did not shorten over a 3-year period, regardless of the age of the individual. Neither telomere length, nor the rate at which the telomeres changed over these 3 years, correlated with breeding frequency or investment. Older females also produced larger volume clutches until approximately 15 years old and larger eggs produced heavier fledglings. Furthermore, reproductive success ( chicks fledged/eggs laid ) is maintained as females aged. Basal corticosterone, however, was not correlated with telomere length in adults and suggests that low basal corticosterone may play a role in the telomere maintenance we observed. Basal corticosterone also declined during the breeding season and was positively correlated with the age of adult penguins. This higher basal corticosterone in older individuals, and consistent reproductive success, supports the prediction that Magellanic penguins invest more in reproduction as they age. Our results

  16. A whole stand basal area projection model for Appalachian hardwoods

    Science.gov (United States)

    John R. Brooks; Lichun Jiang; Matthew Perkowski; Benktesh Sharma

    2008-01-01

    Two whole-stand basal area projection models were developed for Appalachian hardwood stands. The proposed equations are an algebraic difference projection form based on existing basal area and the change in age, trees per acre, and/or dominant height. Average equation error was less than 10 square feet per acre and residuals exhibited no irregular trends.

  17. Two cases of basal cell carcinoma arising from chronic radiation dermatitis

    International Nuclear Information System (INIS)

    Wakamori, Takeshi; Takenaka, Hideya; Ueda, Eiichiro; Katoh, Norito; Kishimoto, Saburo

    2003-01-01

    A 48-year-old female and a 51-year-old male with basal cell carcinoma (BCC) arising from chronic radiation dermatitis are reviewed. They are treated with radiotherapy for hemangioma on their right cheek in their childhood. Review in the literature showed high incidence of the histological diagnosis of malignant skin tumors arising from chronic radiation dermatitis are follows: squamous cell carcinoma (SCC), BCC, sarcoma, and Bowen's disease. (author)

  18. Giant morphea-form basal cell carcinoma of the umbilicus: Successful debulking with vismodegib.

    Science.gov (United States)

    Orduz Robledo, Mariana; Lebas, Eve; Reginster, Marie-Annick; Baghaie, Mahmoud; Groves, Sabine; Nikkels, Arjen F

    2018-01-01

    Basal cell carcinoma of the umbilicus is very rare. The nodular subtype is the main representative. Giant basal cell carcinomas represent around 1% of all basal cell carcinomas. The hedgehog pathway inhibitor vismodegib is indicated for advanced basal cell carcinoma and CD56-negative immunostaining seems indicative for successful treatment. A 54-year-old man presented a 10 cm × 14 cm large and 4.5 cm deep morphea-form basal cell carcinoma with faint immunohistochemical CD56 expression arising from the umbilicus. A sequential treatment was initiated with debulking using vismodegib 150 mg per day for 4 months, followed by reconstructive surgery. To the best of our knowledge, this is the first report of a giant basal cell carcinoma of the morphea-form type of the umbilicus. The sequential treatment plan reduces the duration of vismodegib inherent adverse effects and significantly reduces the tumor mass prior to surgery. Besides increasing adherence to vismodegib treatment, this approach facilitates the surgical technique and improves cosmetic outcome.

  19. Basal Cell Carcinoma in Cases with or without Xeroderma Pigmentosum.

    Science.gov (United States)

    Ghartimagar, Dilasma; Ghosh, Arnab; Shrestha, Sushil Ram; Shrestha, Sachet; Thapa, Sushma; Narasimhan, Raghavan; Talwar, O P

    2017-01-01

    Basal cell carcinoma is the most common form of cancer in humans and comprises the vast majority of skin cancers. It predominantly affects fair-skinned individuals, and its incidence is rapidly increasing. The objective of the study is to identify the epidemiology, its topography and different histological subtypes of basal cell carcinoma in patients with or without Xeroderma Pigmentosum. A cross-sectional descriptive study was conducted at Manipal Teaching Hospital, Pokhara from Jan 2009 to Dec 2016. Ethical approval was taken from MEMG/IRC/GA. The study included patients with a confirmed diagnosis of basal cell carcinoma irrespective of their age and sex. This study showed 77 individuals with 91 biopsies of BCC including 5 cases of Xeroderma Pigmentosum. The predominant histological subtype was nodular with 41 (53.94%) cases, followed by the 14 (18.42%) cases of pigmented and 10 (13.15%) cases baso-squamous subtype. The most frequent sites of involvement were the head and neck, with predominance in the nasal and orbital region. The mean age was 57.68 years but the basal cell carcinoma in cases of Xeroderma Pigmentosum was seen more in younger age groups. There were 43 (55.84 %) male patients and 34 (44.16 %) female patients with a male to female ratio of 1.26:1. Nodular and pigmented varieties were the most frequent subtypes with nose being the commonest site of involvement. Basal cell carcinomas in cases of Xeroderma Pigmentosum were noted in younger age group with multiple lesions.

  20. Basal Cell Carcinoma with Myoepithelial Differentiation: Case Report and Literature Review.

    Science.gov (United States)

    Cohen, Philip R

    2018-01-17

    Basal cell carcinoma is the most common skin cancer. Myoepithelial cells are specialized epithelial cells. Basal cell carcinoma with myoepithelial differentiation is a rare tumor. A 71-year-old man with a basal cell carcinoma with myoepithelial differentiation that presented as an asymptomatic red papule of two months duration on his forehead is described. Including the reported patient, this variant of basal cell carcinoma has been described in 16 patients: 11 men and five women. The patients ranged in age at diagnosis from 43 years to 83 years; the median age at diagnosis was 66 years. All of the tumors were located on the face-most were papules or nodules of less than 10 x 10 mm. Their pathology demonstrated two components: one was that of a typical basal cell carcinoma and the other was myoepithelioma-like in which the tumor cells were plasmacytoid or signet ring in appearance and contained abundant eosinophilic cytoplasm or hyaline inclusions or both. The myoepithelial tumor cells had variable immunohistochemical expression that included not only cytokeratin but also actin, glial fibrillary acid protein, S100, and vimentin. The most common clinical impression, prior to biopsy, was a basal cell carcinoma. The pathologic differential diagnosis included cutaneous mixed sweat gland tumor of the skin, myoepithelioma, myoepithelial carcinoma, and tumors that contain a prominent signet ring cell component (such as metastatic gastrointestinal and breast carcinoma, melanoma, plasmacytoid squamous cell carcinoma, and T-cell lymphoma). Mohs micrographic surgical excision, with complete removal of the tumor, was recommended for treatment of the carcinoma.

  1. The role of basal ganglia in language production: evidence from Parkinson's disease.

    Science.gov (United States)

    Macoir, Joël; Fossard, Marion; Mérette, Chantal; Langlois, Mélanie; Chantal, Sophie; Auclair-Ouellet, Noémie

    2013-01-01

    According to the dominant view in the literature, basal ganglia do not play a direct role in language but are involved in cognitive control required by linguistic and non-linguistic processing. In Parkinson's disease, basal ganglia impairment leads to motor symptoms and language deficits; those affecting the production of verbs have been frequently explored. According to a controversial theory, basal ganglia play a specific role in the conjugation of regular verbs as compared to irregular verbs. We report the results of 15 patients with Parkinson's disease in experimental conjugation tasks. They performed below healthy controls but their performance did not differ for regular and irregular verbs. These results confirm that basal ganglia are involved in language processing but do not play a specific role in verb production.

  2. Metastatic basal cell carcinoma caused by carcinoma misdiagnosed as acne - case report and literature review

    DEFF Research Database (Denmark)

    Aydin, Dogu; Hölmich, Lisbet Rosenkrantz; Jakobsen, Linda Plovmand

    2016-01-01

    Basal cell carcinoma can be misdiagnosed as acne; thus, carcinoma should be considered in treatment-resistant acne. Although rare, neglected basal cell carcinoma increases the risk of metastasis.......Basal cell carcinoma can be misdiagnosed as acne; thus, carcinoma should be considered in treatment-resistant acne. Although rare, neglected basal cell carcinoma increases the risk of metastasis....

  3. Sas-4 proteins are required during basal body duplication in Paramecium

    Science.gov (United States)

    Gogendeau, Delphine; Hurbain, Ilse; Raposo, Graca; Cohen, Jean; Koll, France; Basto, Renata

    2011-01-01

    Centrioles and basal bodies are structurally related organelles composed of nine microtubule (MT) triplets. Studies performed in Caenorhabditis elegans embryos have shown that centriole duplication takes place in sequential way, in which different proteins are recruited in a specific order to assemble a procentriole. ZYG-1 initiates centriole duplication by triggering the recruitment of a complex of SAS-5 and SAS-6, which then recruits the final player, SAS-4, to allow the incorporation of MT singlets. It is thought that a similar mechanism (that also involves additional proteins) is present in other animal cells, but it remains to be investigated whether the same players and their ascribed functions are conserved during basal body duplication in cells that exclusively contain basal bodies. To investigate this question, we have used the multiciliated protist Paramecium tetraurelia. Here we show that in the absence of PtSas4, two types of defects in basal body duplication can be identified. In the majority of cases, the germinative disk and cartwheel, the first structures assembled during duplication, are not detected. In addition, if daughter basal bodies were formed, they invariably had defects in MT recruitment. Our results suggest that PtSas4 has a broader function than its animal orthologues. PMID:21289083

  4. Basal insulin analogues in the treatment of diabetes mellitus: What progress have we made?

    OpenAIRE

    Kalra, Sanjay

    2015-01-01

    Over the past few decades, continuous progress has been made in the development of insulin therapy. Basal insulins were developed around 60 years ago. However, existing basal insulins were found to have limitations. An ideal basal insulin should have the following properties viz. longer duration of action, a flat time-action profile, low day-to-day glycaemic variability, and the potential for flexible dosing. Basal insulins have advanced over the years, from lectin and neutral protamine Haged...

  5. Potential side effects of unhealthy lifestyle choices and health risks on basal and reactive heart rate variability in college drinkers.

    Science.gov (United States)

    Udo, Tomoko; Mun, Eun-Young; Buckman, Jennifer F; Vaschillo, Evgeny G; Vaschillo, Bronya; Bates, Marsha E

    2013-09-01

    Emerging adults often begin making independent lifestyle choices during college, yet the association of these choices with fundamental indicators of health and adaptability is unclear. The present study examined the relationship between health risks and neurocardiac function in college drinkers. Heart rate variability (HRV) was assessed at baseline and in reaction to a paced breathing challenge in 212 college drinkers (53.8% women). Basal HRV served as a general indicator of health. Reactive HRV (during paced breathing) was used as a marker of an individual's adaptability to challenge. The relationship of HRV to alcohol use, cigarette use, exercise, sleep, and body mass index (BMI) was assessed. Greater alcohol use and less exercise were associated with lower basal HRV. BMI was unrelated to basal HRV but was negatively associated with reactive HRV during the breathing challenge. High levels of alcohol use and lack of exercise are negative correlates of cardiovascular and general health, even in apparently healthy college drinkers. The negative relationship between BMI and reactive HRV suggests that overweight individuals have reduced ability to psychophysiologically adapt to challenges; understanding the temporal course of this relationship is needed. This study highlights the importance of examining HRV at baseline and in response to a challenge to capture the active neurocardiac processes that contribute to health and adaptive responding. The suppressive effects of health risks on HRV are modifiable; thus, HRV may be useful in evaluating the health benefits of lifestyle change and in promoting change behaviors in college drinkers.

  6. Comparative histochemical study of Bowen’s disease and actinic keratosis: preserved normal basal cells in Bowen’s disease

    Directory of Open Access Journals (Sweden)

    H Ishida

    2009-12-01

    Full Text Available The degree of DNA-instability as revealed by immunohistochemical staining with anti-cytidine antibody after acid hydrolysis (DNA-instability test has been recently used as a marker of malignancy. This technique was applied to examine 17 skin tissue samples of Bowen’s disease, 47 of actinic keratosis, 15 of squamous cell carcinoma, 5 of seborrheic keratosis, and 10 of normal skin. All benign neoplastic cells of seborrheic keratosis and normal epidermal cells were negative. On the other hand, all cancer cells were positive with the DNA-instability test, indicating their malignancy, but all basal cells in Bowen’s disease were completely negative. Compatible with this result, the basal cells in Bowen’s disease were characteristically normal as evident in other histochemical examinations. Thus, they were negative with p53 immunohistochemistry, with normal signals of chromosome 17 in situ hybridisation and argyrophilic nucleolar organiser region, and showed slightly enhanced proliferative activity as revealed by proliferating cell nuclear antigen immunohistochemistry. Immunohistochemical staining with 34 ß E12 (monoclonal antibody against cytokeratins 1, 5, 10, and 14, which stains all normal epidermal keratinocytes including basal cells, showed that only the basal cells of Bowen’s disease stained strongly and homogeneously, while all cancer cells in the upper layers of Bowen’s disease and all layers of actinic keratosis were only sporadically or weakly stained. Staining with 34 ß B4 (monoclonal antibody against cytokeratin 1, which recognises the whole epidermis except for the basal layer in the normal epidermis, showed that the basal cells in the Bowen’s disease were completely negative, and lower layer cells in the actinic keratosis and upper layer cells in Bowen’s disease were only sporadically stained positive, although the superficial layer cells in actinic keratosis stained strongly and homogeneously. Our findings clearly

  7. Psychological Assessment of Patients With Biotin-Thiamine-Responsive Basal Ganglia Disease.

    Science.gov (United States)

    Alfadhel, Majid; Al-Bluwi, Amal

    2017-01-01

    Biotin-thiamine-responsive basal ganglia disease is a devastating autosomal recessive inherited neurological disorder. We conducted a retrospective chart review of all patients with biotin-thiamine-responsive basal ganglia disease who underwent a formal psychological assessment. Six females and 3 males were included. Five patients (56%) had an average IQ, two patients (22%) had mild delay, and two (22%) had severe delay. A normal outcome was directly related to the time of diagnosis and initiation of treatment. Early diagnosis and immediate commencement of treatment were associated with a favorable outcome and vice versa. The most affected domain was visual motor integration, while understanding and mathematical problem-solving were the least affected. In summary, this is the first study discussing the psychological assessment of patients with biotin-thiamine-responsive basal ganglia disease. The results of this study alert clinicians to consider prompt initiation of biotin and thiamine in any patient presenting with neuroregression and a basal ganglia lesion on a brain magnetic resonance imaging.

  8. Variable Basal Melt Rates of Antarctic Peninsula Ice Shelves, 1994-2016

    Science.gov (United States)

    Adusumilli, Susheel; Fricker, Helen Amanda; Siegfried, Matthew R.; Padman, Laurie; Paolo, Fernando S.; Ligtenberg, Stefan R. M.

    2018-05-01

    We have constructed 23-year (1994-2016) time series of Antarctic Peninsula (AP) ice-shelf height change using data from four satellite radar altimeters (ERS-1, ERS-2, Envisat, and CryoSat-2). Combining these time series with output from atmospheric and firn models, we partitioned the total height-change signal into contributions from varying surface mass balance, firn state, ice dynamics, and basal mass balance. On the Bellingshausen coast of the AP, ice shelves lost 84 ± 34 Gt a-1 to basal melting, compared to contributions of 50 ± 7 Gt a-1 from surface mass balance and ice dynamics. Net basal melting on the Weddell coast was 51 ± 71 Gt a-1. Recent changes in ice-shelf height include increases over major AP ice shelves driven by changes in firn state. Basal melt rates near Bawden Ice Rise, a major pinning point of Larsen C Ice Shelf, showed large increases, potentially leading to substantial loss of buttressing if sustained.

  9. [Modern diagnosis and treatment in children with congenital basal encephalocele].

    Science.gov (United States)

    Sakharov, A V; Roginskiy, V V; Kapitanov, D N; Ivanov, A L; Shelesko, E V; Gorelyshev, S K; Evteev, A A; Lemeneva, N V; Zinkevich, D N; Kochkin, Yu A; Ozerova, V I; Satanin, L A

    Basal encephalocele is a rare disease that predominantly occurs in children. Its most common symptoms include nasal liquorrhea, difficulty in nasal breathing, and deformity of the naso-orbital region. The study group included 19 patients with basal encephalocele, aged 2 months to 18 years. Ten (59%) patients were operated on through a transnasal endoscopic approach; 3 (17.5%) patients were operated on through a transcranial approach; 4 (23.5%) patients were operated on using a combined approach: the patients underwent simultaneous elimination of a cranio-orbital region deformity using the basal transcranial approach as well as hernial sac resection and hernioplasty using the transnasal endoscopic approach. Two children had no surgery due to minimal symptoms and a lack of cerebrospinal fluid leak. Application of the algorithms for diagnosis and treatment of encephalocele, suggested by the authors, enabled making the timely diagnose, defining the optimal surgical tactics, and achieving good treatment results. A differentiated approach to the choice of a surgical technique for basal encephalocele, the use of auto-tissues for skull base reconstruction, intraoperative and postoperative lumbar drainage, and simultaneous elimination of deformity of the fronto-naso-orbital region enable avoiding complications and achieving good functional and aesthetic results.

  10. Neglected giant scalp Basal cell carcinoma

    DEFF Research Database (Denmark)

    Larsen, Anne Kristine; El-Charnoubi, Waseem-Asim Ghulam; Gehl, Julie

    2014-01-01

    control, a satisfactory long-term cosmetic and functional result. We present a case with a neglected basal cell scalp carcinoma, treated with wide excision and postoperative radiotherapy, reconstructed with a free latissimus dorsi flap. The cosmetic result is acceptable and there is no sign of recurrence...

  11. Apoplastic Venom Allergen-like Proteins of Cyst Nematodes Modulate the Activation of Basal Plant Innate Immunity by Cell Surface Receptors

    Science.gov (United States)

    Lozano-Torres, Jose L.; Wilbers, Ruud H. P.; Warmerdam, Sonja; Finkers-Tomczak, Anna; Diaz-Granados, Amalia; van Schaik, Casper C.; Helder, Johannes; Bakker, Jaap; Goverse, Aska; Schots, Arjen; Smant, Geert

    2014-01-01

    Despite causing considerable damage to host tissue during the onset of parasitism, nematodes establish remarkably persistent infections in both animals and plants. It is thought that an elaborate repertoire of effector proteins in nematode secretions suppresses damage-triggered immune responses of the host. However, the nature and mode of action of most immunomodulatory compounds in nematode secretions are not well understood. Here, we show that venom allergen-like proteins of plant-parasitic nematodes selectively suppress host immunity mediated by surface-localized immune receptors. Venom allergen-like proteins are uniquely conserved in secretions of all animal- and plant-parasitic nematodes studied to date, but their role during the onset of parasitism has thus far remained elusive. Knocking-down the expression of the venom allergen-like protein Gr-VAP1 severely hampered the infectivity of the potato cyst nematode Globodera rostochiensis. By contrast, heterologous expression of Gr-VAP1 and two other venom allergen-like proteins from the beet cyst nematode Heterodera schachtii in plants resulted in the loss of basal immunity to multiple unrelated pathogens. The modulation of basal immunity by ectopic venom allergen-like proteins in Arabidopsis thaliana involved extracellular protease-based host defenses and non-photochemical quenching in chloroplasts. Non-photochemical quenching regulates the initiation of the defense-related programmed cell death, the onset of which was commonly suppressed by venom allergen-like proteins from G. rostochiensis, H. schachtii, and the root-knot nematode Meloidogyne incognita. Surprisingly, these venom allergen-like proteins only affected the programmed cell death mediated by surface-localized immune receptors. Furthermore, the delivery of venom allergen-like proteins into host tissue coincides with the enzymatic breakdown of plant cell walls by migratory nematodes. We, therefore, conclude that parasitic nematodes most likely utilize

  12. Apoplastic venom allergen-like proteins of cyst nematodes modulate the activation of basal plant innate immunity by cell surface receptors.

    Science.gov (United States)

    Lozano-Torres, Jose L; Wilbers, Ruud H P; Warmerdam, Sonja; Finkers-Tomczak, Anna; Diaz-Granados, Amalia; van Schaik, Casper C; Helder, Johannes; Bakker, Jaap; Goverse, Aska; Schots, Arjen; Smant, Geert

    2014-12-01

    Despite causing considerable damage to host tissue during the onset of parasitism, nematodes establish remarkably persistent infections in both animals and plants. It is thought that an elaborate repertoire of effector proteins in nematode secretions suppresses damage-triggered immune responses of the host. However, the nature and mode of action of most immunomodulatory compounds in nematode secretions are not well understood. Here, we show that venom allergen-like proteins of plant-parasitic nematodes selectively suppress host immunity mediated by surface-localized immune receptors. Venom allergen-like proteins are uniquely conserved in secretions of all animal- and plant-parasitic nematodes studied to date, but their role during the onset of parasitism has thus far remained elusive. Knocking-down the expression of the venom allergen-like protein Gr-VAP1 severely hampered the infectivity of the potato cyst nematode Globodera rostochiensis. By contrast, heterologous expression of Gr-VAP1 and two other venom allergen-like proteins from the beet cyst nematode Heterodera schachtii in plants resulted in the loss of basal immunity to multiple unrelated pathogens. The modulation of basal immunity by ectopic venom allergen-like proteins in Arabidopsis thaliana involved extracellular protease-based host defenses and non-photochemical quenching in chloroplasts. Non-photochemical quenching regulates the initiation of the defense-related programmed cell death, the onset of which was commonly suppressed by venom allergen-like proteins from G. rostochiensis, H. schachtii, and the root-knot nematode Meloidogyne incognita. Surprisingly, these venom allergen-like proteins only affected the programmed cell death mediated by surface-localized immune receptors. Furthermore, the delivery of venom allergen-like proteins into host tissue coincides with the enzymatic breakdown of plant cell walls by migratory nematodes. We, therefore, conclude that parasitic nematodes most likely utilize

  13. Apoplastic venom allergen-like proteins of cyst nematodes modulate the activation of basal plant innate immunity by cell surface receptors.

    Directory of Open Access Journals (Sweden)

    Jose L Lozano-Torres

    2014-12-01

    Full Text Available Despite causing considerable damage to host tissue during the onset of parasitism, nematodes establish remarkably persistent infections in both animals and plants. It is thought that an elaborate repertoire of effector proteins in nematode secretions suppresses damage-triggered immune responses of the host. However, the nature and mode of action of most immunomodulatory compounds in nematode secretions are not well understood. Here, we show that venom allergen-like proteins of plant-parasitic nematodes selectively suppress host immunity mediated by surface-localized immune receptors. Venom allergen-like proteins are uniquely conserved in secretions of all animal- and plant-parasitic nematodes studied to date, but their role during the onset of parasitism has thus far remained elusive. Knocking-down the expression of the venom allergen-like protein Gr-VAP1 severely hampered the infectivity of the potato cyst nematode Globodera rostochiensis. By contrast, heterologous expression of Gr-VAP1 and two other venom allergen-like proteins from the beet cyst nematode Heterodera schachtii in plants resulted in the loss of basal immunity to multiple unrelated pathogens. The modulation of basal immunity by ectopic venom allergen-like proteins in Arabidopsis thaliana involved extracellular protease-based host defenses and non-photochemical quenching in chloroplasts. Non-photochemical quenching regulates the initiation of the defense-related programmed cell death, the onset of which was commonly suppressed by venom allergen-like proteins from G. rostochiensis, H. schachtii, and the root-knot nematode Meloidogyne incognita. Surprisingly, these venom allergen-like proteins only affected the programmed cell death mediated by surface-localized immune receptors. Furthermore, the delivery of venom allergen-like proteins into host tissue coincides with the enzymatic breakdown of plant cell walls by migratory nematodes. We, therefore, conclude that parasitic nematodes

  14. Proximal tubule-specific glutamine synthetase deletion alters basal and acidosis-stimulated ammonia metabolism

    Science.gov (United States)

    Lee, Hyun-Wook; Osis, Gunars; Handlogten, Mary E.; Lamers, Wouter H.; Chaudhry, Farrukh A.; Verlander, Jill W.

    2016-01-01

    Glutamine synthetase (GS) catalyzes the recycling of NH4+ with glutamate to form glutamine. GS is highly expressed in the renal proximal tubule (PT), suggesting ammonia recycling via GS could decrease net ammoniagenesis and thereby limit ammonia available for net acid excretion. The purpose of the present study was to determine the role of PT GS in ammonia metabolism under basal conditions and during metabolic acidosis. We generated mice with PT-specific GS deletion (PT-GS-KO) using Cre-loxP techniques. Under basal conditions, PT-GS-KO increased urinary ammonia excretion significantly. Increased ammonia excretion occurred despite decreased expression of key proteins involved in renal ammonia generation. After the induction of metabolic acidosis, the ability to increase ammonia excretion was impaired significantly by PT-GS-KO. The blunted increase in ammonia excretion occurred despite greater expression of multiple components of ammonia generation, including SN1 (Slc38a3), phosphate-dependent glutaminase, phosphoenolpyruvate carboxykinase, and Na+-coupled electrogenic bicarbonate cotransporter. We conclude that 1) GS-mediated ammonia recycling in the PT contributes to both basal and acidosis-stimulated ammonia metabolism and 2) adaptive changes in other proteins involved in ammonia metabolism occur in response to PT-GS-KO and cause an underestimation of the role of PT GS expression. PMID:27009341

  15. Nevoid basal cell carcinoma syndrome. Profile of genetic and environmental factors in oncogenesis

    International Nuclear Information System (INIS)

    Howell, J.B.

    1984-01-01

    Nevoid basal cell carcinomas (NBCCs) are a prototype of a genetic form of basal cell carcinoma. These basal cell cancers, rather than being caused by genetic factors alone, are most likely the product of genetic and environmental factors. The NBCC syndrome provides a model for studying tumors induced by ionizing radiation and for viewing carcinogenesis as a multistage process explainable by a minimum of two steps. The interaction of genetic and environmental factors in producing tumors to which an individual is predisposed can be studied in patients with the NBCC syndrome and childhood medulloblastoma that was treated by radiation therapy. Individuals with the NBCC syndrome represent a special subgroup with a hereditary predisposition to basal cell carcinoma in whom ionizing radiation may supply the subsequent mutation necessary for tumor development. The genetically altered epidermis underlying the palm and sole pits found in patients with the syndrome represents basal cell carcinoma in situ from which basal cell carcinomas develop, albeit infrequently. The restrained biologic behavior of most of these tumors contrasts with the usual destructive behavior of the NBCCs of the head and neck in the same patient

  16. Past, present and future of the pathophysiological model of the basal ganglia

    Directory of Open Access Journals (Sweden)

    Jose A Obeso

    2011-07-01

    Full Text Available The current model of basal ganglia was introduced two decades ago and has settled most of our current understanding of basal ganglia function and dysfunction. Extensive research efforts have been carried out in recent years leading to further refinement and understanding of the normal and diseased basal ganglia. Several questions, however, are yet to be resolved. This short review provides a synopsis of the evolution of thought regarding the pathophysiological model of the BG and summarizes the main recent findings and additions to this field of research. We have also tried to identify major challenges that need to be addressed and resolved in the near future. Detailed accounts and state-of-the-art developments concerning research on the basal ganglia are provided in the articles that make up this Special Issue.

  17. Creation of computerized 3D MRI-integrated atlases of the human basal ganglia and thalamus

    Directory of Open Access Journals (Sweden)

    Abbas F. Sadikot

    2011-09-01

    Full Text Available Functional brain imaging and neurosurgery in subcortical areas often requires visualization of brain nuclei beyond the resolution of current Magnetic Resonance Imaging (MRI methods. We present techniques used to create: 1 a lower resolution 3D atlas, based on the Schaltenbrand and Wahren print atlas, which was integrated into a stereotactic neurosurgery planning and visualization platform (VIPER; and 2 a higher resolution 3D atlas derived from a single set of manually segmented histological slices containing nuclei of the basal ganglia, thalamus, basal forebrain and medial temporal lobe. Both atlases were integrated to a canonical MRI (Colin27 from a young male participant by manually identifying homologous landmarks. The lower resolution atlas was then warped to fit the MRI based on the identified landmarks. A pseudo-MRI representation of the high-resolution atlas was created, and a nonlinear transformation was calculated in order to match the atlas to the template MRI. The atlas can then be warped to match the anatomy of Parkinson’s disease surgical candidates by using 3D automated nonlinear deformation methods. By way of functional validation of the atlas, the location of the sensory thalamus was correlated with stereotactic intraoperative physiological data. The position of subthalamic electrode positions in patients with Parkinson’s disease was also evaluated in the atlas-integrated MRI space. Finally, probabilistic maps of subthalamic stimulation electrodes were developed, in order to allow group analysis of the location of contacts associated with the best motor outcomes. We have therefore developed, and are continuing to validate, a high-resolution computerized MRI-integrated 3D histological atlas, which is useful in functional neurosurgery, and for functional and anatomical studies of the human basal ganglia, thalamus and basal forebrain.

  18. Basal Cell Carcinoma Arising in a Breast Augmentation Scar.

    Science.gov (United States)

    Edwards, Lisa R; Cresce, Nicole D; Russell, Mark A

    2017-04-01

    We report a case of a 46-year-old female who presented with a persistent lesion on the inferior right breast. The lesion was located within the scar from a breast augmentation procedure 12 years ago. The lesion had been treated as several conditions with no improvement. Biopsy revealed a superficial and nodular basal cell carcinoma, and the lesion was successfully removed with Mohs micrographic surgery. Basal cell carcinoma arising in a surgical scar is exceedingly rare with only 13 reported cases to date. This is the first reported case of basal cell carcinoma arising in a breast augmentation scar. We emphasize the importance of biopsy for suspicious lesions or those refractory to treatment, particularly those lesions that form within a scar. Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

  19. Understanding Ice Shelf Basal Melting Using Convergent ICEPOD Data Sets: ROSETTA-Ice Study of Ross Ice Shelf

    Science.gov (United States)

    Bell, R. E.; Frearson, N.; Tinto, K. J.; Das, I.; Fricker, H. A.; Siddoway, C. S.; Padman, L.

    2017-12-01

    The future stability of the ice shelves surrounding Antarctica will be susceptible to increases in both surface and basal melt as the atmosphere and ocean warm. The ROSETTA-Ice program is targeted at using the ICEPOD airborne technology to produce new constraints on Ross Ice Shelf, the underlying ocean, bathymetry, and geologic setting, using radar sounding, gravimetry and laser altimetry. This convergent approach to studying the ice-shelf and basal processes enables us to develop an understanding of the fundamental controls on ice-shelf evolution. This work leverages the stratigraphy of the ice shelf, which is detected as individual reflectors by the shallow-ice radar and is often associated with surface scour, form close to the grounding line or pinning points on the ice shelf. Surface accumulation on the ice shelf buries these reflectors as the ice flows towards the calving front. This distinctive stratigraphy can be traced across the ice shelf for the major East Antarctic outlet glaciers and West Antarctic ice streams. Changes in the ice thickness below these reflectors are a result of strain and basal melting and freezing. Correcting the estimated thickness changes for strain using RIGGS strain measurements, we can develop decadal-resolution flowline distributions of basal melt. Close to East Antarctica elevated melt-rates (>1 m/yr) are found 60-100 km from the calving front. On the West Antarctic side high melt rates primarily develop within 10 km of the calving front. The East Antarctic side of Ross Ice Shelf is dominated by melt driven by saline water masses that develop in Ross Sea polynyas, while the melting on the West Antarctic side next to Hayes Bank is associated with modified Continental Deep Water transported along the continental shelf. The two sides of Ross Ice Shelf experience differing basal melt in part due to the duality in the underlying geologic structure: the East Antarctic side consists of relatively dense crust, with low amplitude

  20. Basal cell carcinoma of the nipple - an unusual location in a male patient.

    Science.gov (United States)

    Avci, Oktay; Pabuççuoğlu, Uğur; Koçdor, M Ali; Unlü, Mehtat; Akin, Ciler; Soyal, Cüneyt; Canda, Tülay

    2008-02-01

    Although basal cell carcinoma is extremely common, it only rarely occurs on the nipple. Men are affected more often than women. Basal cell carcinoma of the nipple-areola complex may be more aggressive as metastases to regional lymph nodes have been reported. We report a basal cell carcinoma of the nipple with features of a fibroepithelioma of Pinkus in a man and review the literature.

  1. The Stress Model of Chronic Pain: Evidence from Basal Cortisol and Hippocampal Structure and Function in Humans

    Science.gov (United States)

    Vachon-Presseau, Etienne; Roy, Mathieu; Martel, Marc-Olivier; Caron, Etienne; Marin, Marie-France; Chen, Jeni; Albouy, Genevieve; Plante, Isabelle; Sullivan, Michael J.; Lupien, Sonia J.; Rainville, Pierre

    2013-01-01

    Recent theories have suggested that chronic pain could be partly maintained by maladaptive physiological responses of the organism facing a recurrent stressor. The present study examined the associations between basal levels of cortisol collected over seven consecutive days, the hippocampal volumes and brain activation to thermal stimulations…

  2. Basal cell carcinoma of the skin with areas of squamous cell carcinoma: a basosquamous cell carcinoma?

    OpenAIRE

    de Faria, J

    1985-01-01

    The diagnosis of basosquamous cell carcinoma is controversial. A review of cases of basal cell carcinoma showed 23 cases that had conspicuous areas of squamous cell carcinoma. This was distinguished from squamous differentiation and keratotic basal cell carcinoma by a comparative study of 40 cases of compact lobular and 40 cases of keratotic basal cell carcinoma. Areas of intermediate tumour differentiation between basal cell and squamous cell carcinoma were found. Basal cell carcinomas with ...

  3. Effect of calorie restriction on spontaneous physical activity and body mass in mice divergently selected for basal metabolic rate (BMR).

    Science.gov (United States)

    Brzęk, Paweł; Gębczyński, Andrzej K; Książek, Aneta; Konarzewski, Marek

    2016-07-01

    Spontaneous physical activity (SPA) represents an important component of daily energy expenditures in animals and humans. Intra-specific variation in SPA may be related to the susceptibility to metabolic disease or obesity. In particular, reduced SPA under conditions of limited food availability may conserve energy and prevent loss of body and fat mass ('thrifty genotype hypothesis'). However, both SPA and its changes during food restriction show wide inter-individual variations. We studied the effect of 30% caloric restriction (CR) on SPA in laboratory mice divergently selected for high (H-BMR) and low (L-BMR) basal metabolic rate. Selection increased SPA in the H-BMR line but did not change it in the L-BMR mice. This effect reflected changes in SPA intensity but not SPA duration. CR increased SPA intensity more strongly in the L-BMR line than in the H-BMR line and significantly modified the temporal variation of SPA. However, the initial between-line differences in SPA were not affected by CR. Loss of body mass during CR did not differ between both lines. Our results show that the H-BMR mice can maintain their genetically determined high SPA under conditions of reduced food intake without sacrificing their body mass. We hypothesize that this pattern may reflect the higher flexibility in the energy budget in the H-BMR line, as we showed previously that mice from this line reduced their BMR during CR. These energy savings may allow for the maintenance of elevated SPA in spite of reduced food intake. We conclude that the effect of CR on SPA is in large part determined by the initial level of BMR, whose variation may account for the lack of universal pattern of behavioural responses to CR. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Endocannabinergic modulation of interleukin-1β in mouse hippocampus under basal conditions and after in vivo systemic lipopolysaccharide stimulation.

    Science.gov (United States)

    Csölle, Cecília; Sperlágh, Beáta

    2011-01-01

    Cannabinoids play an important role in the suppression of proinflammatory cytokine production in the periphery and brain. In this study, we explored whether endogenous activation of cannabinoid (CB) 1 receptors (CB1Rs) affects interleukin (IL)-1β levels in the mouse hippocampus under basal conditions and following stimulation with in vivo bacterial lipopolysaccharide (LPS, 250 μg/kg i.p.). IL-1β levels were determined in the hippocampi of wild-type (WT), CB1R-/- and P2X₇ receptor (P2X₇R)-/- mice using an ELISA kit. Basal but not LPS-induced IL-1β levels were downregulated when CB1R function was abrogated by genetic deletion, suggesting that endocannabinoids contributed to basal IL-1β content in the mouse hippocampus. AM251 (3 mg/kg i.p.), an antagonist of CB1Rs, also inhibited basal IL-1β protein in WT but not in CB1R-/- mice. In the absence of P2X₇R, LPS-induced IL-1β production was lower, while the inhibitory effect of CB1R antagonists on basal IL-1β was significantly attenuated. The LPS-induced elevation in IL-1β production was decreased in the presence of AM251 and AM281, with no significant difference between WT and P2X₇R-/- mice. CB1Rs are responsible for the modulation of basal IL-1β levels in the hippocampus, while the effects of CB1 antagonists on systemic LPS-induced IL-1β concentrations are independent of CB1Rs. Copyright © 2011 S. Karger AG, Basel.

  5. Effects of cyclooxygenase and lipoxygenase inhibition on basal- and serotonin-induced ion transport in rat colon

    DEFF Research Database (Denmark)

    Engelmann, Bodil Elisabeth; Bindslev, Niels; Poulsen, Steen Seier

    2002-01-01

    basal conditions. Furthermore, data suggest neither the COX-1 nor the COX-2 enzyme to be of major importance for 5-HT-induced ion transport in rat colon in vitro. In conclusion, this study supports 5-HT as a mediator of chloride secretion by activating several receptor subtypes and the LOX enzyme...

  6. Network effects of subthalamic deep brain stimulation drive a unique mixture of responses in basal ganglia output.

    Science.gov (United States)

    Humphries, Mark D; Gurney, Kevin

    2012-07-01

    Deep brain stimulation (DBS) is a remarkably successful treatment for the motor symptoms of Parkinson's disease. High-frequency stimulation of the subthalamic nucleus (STN) within the basal ganglia is a main clinical target, but the physiological mechanisms of therapeutic STN DBS at the cellular and network level are unclear. We set out to begin to address the hypothesis that a mixture of responses in the basal ganglia output nuclei, combining regularized firing and inhibition, is a key contributor to the effectiveness of STN DBS. We used our computational model of the complete basal ganglia circuit to show how such a mixture of responses in basal ganglia output naturally arises from the network effects of STN DBS. We replicated the diversification of responses recorded in a primate STN DBS study to show that the model's predicted mixture of responses is consistent with therapeutic STN DBS. We then showed how this 'mixture of response' perspective suggests new ideas for DBS mechanisms: first, that the therapeutic frequency of STN DBS is above 100 Hz because the diversification of responses exhibits a step change above this frequency; and second, that optogenetic models of direct STN stimulation during DBS have proven therapeutically ineffective because they do not replicate the mixture of basal ganglia output responses evoked by electrical DBS. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  7. Immunosuppressive Environment in Basal Cell Carcinoma

    DEFF Research Database (Denmark)

    Omland, Silje Haukali; Nielsen, Patricia S; Gjerdrum, Lise M R

    2016-01-01

    Interaction between tumour survival tactics and anti-tumour immune response is a major determinant for cancer growth. Regulatory T cells (T-regs) contribute to tumour immune escape, but their role in basal cell carcinoma (BCC) is not understood. The fraction of T-regs among T cells was analysed b...

  8. Apico-basal polarity complex and cancer

    Indian Academy of Sciences (India)

    Loss of cell polarity is a hallmark for carcinoma, and its underlying molecular mechanism is beginning to emerge from studies on model organisms and cancer cell lines. Moreover, deregulated expression of apico-basal polarity complex components has been reported in human tumours. In this review, we provide an ...

  9. Nevoid Basal Cell Carcinoma Syndrome : A Case Report

    Directory of Open Access Journals (Sweden)

    K Rajanikanth

    2004-01-01

    Full Text Available The nevoid basal cell carcinoma syndrome (NBCCS or Gorlin - Goltz syndrome is an autosomal disorder principally characterized by cutaneous basal cell carcinomas, multiple keratocysts, and skeletal anomalies. The major organ systems involved are skin, bones, central nervous system, eyes, gonads and endocrine. This particular syndrome is extensively described in the literature under different names. However, there are only few cases reported in the Indian literature. An unusual case of a 33-year old male with large odontogenic keratocyst involving impacted canine in the mandible, along with multiple cysts and impacted teeth in the maxilla; bifid rib and vertebral anomalies has been described.

  10. Expression of heparanase in basal cell carcinoma and squamous cell carcinoma.

    Science.gov (United States)

    Pinhal, Maria Aparecida Silva; Almeida, Maria Carolina Leal; Costa, Alessandra Scorse; Theodoro, Thérèse Rachell; Serrano, Rodrigo Lorenzetti; Machado, Carlos D'Apparecida Santos

    2016-01-01

    Heparanase is an enzyme that cleaves heparan sulfate chains. Oligosaccharides generated by heparanase induce tumor progression. Basal cell carcinoma and squamous cell carcinoma comprise types of nonmelanoma skin cancer. Evaluate the glycosaminoglycans profile and expression of heparanase in two human cell lines established in culture, immortalized skin keratinocyte (HaCaT) and squamous cell carcinoma (A431) and also investigate the expression of heparanase in basal cell carcinoma, squamous cell carcinoma and eyelid skin of individuals not affected by the disease (control). Glycosaminoglycans were quantified by electrophoresis and indirect ELISA method. The heparanase expression was analyzed by quantitative RT-PCR (qRTPCR). The A431 strain showed significant increase in the sulfated glycosaminoglycans, increased heparanase expression and decreased hyaluronic acid, comparing to the HaCaT lineage. The mRNA expression of heparanase was significantly higher in Basal cell carcinoma and squamous cell carcinoma compared with control skin samples. It was also observed increased heparanase expression in squamous cell carcinoma compared to the Basal cell carcinoma. The glycosaminoglycans profile, as well as heparanase expression are different between HaCaT and A431 cell lines. The increased expression of heparanase in Basal cell carcinoma and squamous cell carcinoma suggests that this enzyme could be a marker for the diagnosis of such types of non-melanoma cancers, and may be useful as a target molecule for future alternative treatment.

  11. HIGHLY MICROBIAL RESISTANT GRAPHEME OXIDE NANOPARTICLES: SYNTHESIS, CHARACTERIZATION AND ITS ANTIBACTERIAL ACTIVITY

    OpenAIRE

    Vijaylaxmee Mishra; Richa Sharma

    2014-01-01

    The present work deigned to prepare graphene oxide nanoparticles and their antimicrobial activity has been evaluated. Graphene oxide is a singal layer of carbon arranged in a hexagonal pattern the basal planes and the edges of graphene oxide nanoparticles contain functional exogenous groups such as hydroxyl, carbonyl and epoxy group, which not only expand the interlayer distance but also make the atomic thick layer hydrophilic. Most important application in area related to transparent conduct...

  12. In-pot evaluation of different composted and pelletized organic fertilizers on soil carbon dioxide efflux and basal respiration

    Science.gov (United States)

    Opsi, Francesca; Cavallo, Eugenio; Cocco, Stefania; Corti, Giuseppe

    2013-04-01

    Climate change is one of the most important environmental problems and it is closely related to concentration changes of greenhouse gases (GHG) in the atmosphere, mainly due to anthropogenic activities. As a consequence, measures have been taken to reduce GHG emissions, some of which are associated with agriculture, as well as to the enhancement of soil carbon storage. Modern intensive farming activities have also raised problems related to the safe disposal of large volume of animal waste, such as pig slurry, where the excessive land spreading can lead to water pollution and GHG evolution to the atmosphere. Composting is a great environmentally sustainable option for recycling agricultural by-products, and pelletisation is a promising technology to reduce the large volume of mature composted material in pelleted fertilizers, more suitable for long-distance transport. This study consisted of a pot-incubation experience carried out in a greenhouse of the National Research Council of Italy, under controlled conditions. The aim of the research was to investigate the effect of a composted swine solid fraction (CS, 13% w/w) and swine solid fraction blended with sawdust and composted (CSS, 9% w/w), both also as a result of pelletisation process (CSP, 12% w/w and CSSP, 8% w/w, respectively), on soil organic matter mineralization and basal respiration. Results were obtained by monitoring CO2 efflux, basal respiration and microbial biomass C on amended soil, freshly collected in a vineyard planted on a Typic Ustorthent, fine-loamy, mixed, calcareous, mesic. Samples, adjusted and maintained to about 50-60% of water holding capacity, were conditioned at 25±3 °C for 31 days of incubation. The CO2 fluxes showed a high production at the initial stage of incubation, where differences among treatments were well-rendered. CSSP produced the highest values, while CSS showed values as lower as about 45%. Intermediate values, and similar to those found in the soil sample used as

  13. Basal encephalocele associated with morning glory syndrome: case report Encefalocele basal associada a síndrome "morning glory": relato de caso

    Directory of Open Access Journals (Sweden)

    Ivanete Minotto

    2007-12-01

    Full Text Available The basal encephaloceles refer to rare entities and they correspond to herniation of brain tissue through defects of skull along the cribiform plate or the sphenoid bone. A rare morning glory syndrome, with characteristic retinal defect has been reported in association with basal encephaloceles. Hypophysis hormonal deficiencies may occur. We accounted for a pituitary dwarfism with delayed diagnosed transsphenoidal encephalocele associated with morning glory syndrome, showing the alterations found in retinography, computed tomography and magnetic resonance imaging.As encefaloceles basais são entidades raras e correspondem a herniações do tecido cerebral através de um defeito do crânio, ao longo da lâmina crivosa etmoidal ou do osso esfenoidal. A rara síndrome morning glory, com alterações de fundo de olho características pode apresentar-se associada à encefalocele basal. Deficiências hormonais hipofisárias podem ocorrer. Relatamos caso de nanismo hipofisário com encefalocele transesfenoidal de diagnóstico tardio associada à síndrome de morning glory, mostrando as alterações na retinografia, tomografia computadorizada e ressonância magnética.

  14. Aberrant functional connectivity within the basal ganglia of patients with Parkinson's disease.

    Science.gov (United States)

    Rolinski, Michal; Griffanti, Ludovica; Szewczyk-Krolikowski, Konrad; Menke, Ricarda A L; Wilcock, Gordon K; Filippini, Nicola; Zamboni, Giovanna; Hu, Michele T M; Mackay, Clare E

    2015-01-01

    Resting state functional MRI (rs-fMRI) has been previously shown to be a promising tool for the assessment of early Parkinson's disease (PD). In order to assess whether changes within the basal ganglia network (BGN) are disease specific or relate to neurodegeneration generally, BGN connectivity was assessed in 32 patients with early PD, 19 healthy controls and 31 patients with Alzheimer's disease (AD). Voxel-wise comparisons demonstrated decreased connectivity within the basal ganglia of patients with PD, when compared to patients with AD and healthy controls. No significant changes within the BGN were seen in AD, when compared to healthy controls. Moreover, measures of functional connectivity extracted from regions within the basal ganglia were significantly lower in the PD group. Consistent with previous radiotracer studies, the greatest change when compared to the healthy control group was seen in the posterior putamen of PD subjects. When combined into a single component score, this method differentiated PD from AD and healthy control subjects, with a diagnostic accuracy of 81%. Rs-fMRI can be used to demonstrate the aberrant functional connectivity within the basal ganglia of patients with early PD. These changes are likely to be representative of patho-physiological basal ganglia dysfunction and are not associated with generalised neurodegeneration seen in AD. Further studies are necessary to ascertain whether this method is sensitive enough to detect basal ganglia dysfunction in prodromal PD, and its utility as a potential diagnostic biomarker for premotor and early motoric disease.

  15. Basal-bolus insulin therapy reduces maternal triglycerides in gestational diabetes without modifying cholesteryl ester transfer protein activity.

    Science.gov (United States)

    Olmos, Pablo R; Borzone, Gisella R

    2017-09-01

    Macrosomia in the offspring of overweight/obese mothers with glucose-controlled gestational diabetes mellitus (GDM) is due to excessive rise of maternal triglycerides (TG). We aimed to ascertain whether basal-bolus insulin therapy (BBIT), or other components of the treatment, could reduce TG in GDM. We studied the records of 131 singleton pregnancies with GDM, using stepwise multiple linear regression, Mann-Whitney, χ 2 , and Jonckheere-Terpstra tests. As maternal TG increased steadily during normal pregnancy, these were transformed as z-scores. The atherogenic index of plasma (AIP) was calculated as a measure of cholesteryl ester transfer protein activity. Multiple regression showed that only BBIT (but neither limitation of weight gain nor metformin) reduced maternal TG z-scores (P = 0.011). When the 131 pregnancies were split into two groups - without BBIT (n = 58; HbA1c = 5.3 ± 0.3%) and with BBIT (n = 73; HbA1c = 5.4 ± 0.6; P = 0.2005) - we observed that BBIT (n = 73) reduced maternal TG z-scores in a dose-related fashion (Jonckheere-Terpstra P = 0.03817). The atherogenic index of plasma remained within normal range in both groups. BBIT (but not weight gain control nor metformin) reduced maternal TG in mothers with glucose-controlled GDM. This beneficial effect of BBIT was not related to changes in the cholesteryl ester transfer protein activity. © 2017 Japan Society of Obstetrics and Gynecology.

  16. Arctic Sea Ice Basal Melt Onset Variability and Associated Ocean Surface Heating

    Science.gov (United States)

    Merrick, R. A.; Hutchings, J. K.

    2015-12-01

    The interannual and regional variability in Arctic sea ice melt has previously been characterized only in terms of surface melting. A focus on the variability in the onset of basal melt is additionally required to understand Arctic melt patterns. Monitoring basal melt provides a glimpse into the importance of ocean heating to sea ice melt. This warming is predominantly through seawater exposure due to lead opening and the associated solar warming at the ocean's surface. We present the temporal variability in basal melt onset observed by ice mass balance buoys throughout the Arctic Ocean since 2003, providing a different perspective than the satellite microwave data used to measure the onset of surface melt. We found that melt onset varies greatly, even for buoys deployed within 100km of each other. Therefore large volumes of data are necessary to accurately estimate the variability of basal melt onset. Once the variability of basal melt onset has been identified, we can investigate how this range has been changing as a response to atmospheric and oceanic warming, changes in ice morphology as well as the intensification of the ice albedo feedback.

  17. A basal magma ocean dynamo to explain the early lunar magnetic field

    Science.gov (United States)

    Scheinberg, Aaron L.; Soderlund, Krista M.; Elkins-Tanton, Linda T.

    2018-06-01

    The source of the ancient lunar magnetic field is an unsolved problem in the Moon's evolution. Theoretical work invoking a core dynamo has been unable to explain the magnitude of the observed field, falling instead one to two orders of magnitude below it. Since surface magnetic field strength is highly sensitive to the depth and size of the dynamo region, we instead hypothesize that the early lunar dynamo was driven by convection in a basal magma ocean formed from the final stages of an early lunar magma ocean; this material is expected to be dense, radioactive, and metalliferous. Here we use numerical convection models to predict the longevity and heat flow of such a basal magma ocean and use scaling laws to estimate the resulting magnetic field strength. We show that, if sufficiently electrically conducting, a magma ocean could have produced an early dynamo with surface fields consistent with the paleomagnetic observations.

  18. Glacier surge mechanism based on linked cavity configuration of the basal water conduit system

    Science.gov (United States)

    Kamb, Barclay

    1987-08-01

    Based on observations of the 1982-1983 surge of Variegated Glacier, Alaska, a model of the surge mechanism is developed in terms of a transition from the normal tunnel configuration of the basal water conduit system to a linked cavity configuration that tends to restrict the flow of water, resulting in increased basal water pressures that cause rapid basal sliding. The linked cavity system consists of basal cavities formed by ice-bedrock separation (cavitation), ˜1 m high and ˜10 m in horizontal dimensions, widely scattered over the glacier bed, and hydraulically linked by narrow connections where separation is minimal (separation gap ≲ 0.1 m). The narrow connections, called orifices, control the water flow through the conduit system; by throttling the flow through the large cavities, the orifices keep the water flux transmitted by the basal water system at normal levels even though the total cavity cross-sectional area (˜200 m2) is much larger than that of a tunnel system (˜10 m2). A physical model of the linked cavity system is formulated in terms of the dimensions of the "typical" cavity and orifice and the numbers of these across the glacier width. The model concentrates on the detailed configuration of the typical orifice and its response to basal water pressure and basal sliding, which determines the water flux carried by the system under given conditions. Configurations are worked out for two idealized orifice types, step orifices that form in the lee of downglacier-facing bedrock steps, and wave orifices that form on the lee slopes of quasisinusoidal bedrock waves and are similar to transverse "N channels." The orifice configurations are obtained from the results of solutions of the basal-sliding-with-separation problem for an ice mass constituting of linear half-space of linear rheology, with nonlinearity introduced by making the viscosity stress-dependent on an intuitive basis. Modification of the orifice shapes by melting of the ice roof due to

  19. Activation of Basal Gluconeogenesis by Coactivator p300 Maintains Hepatic Glycogen Storage

    Science.gov (United States)

    Cao, Jia; Meng, Shumei; Ma, Anlin; Radovick, Sally; Wondisford, Fredric E.

    2013-01-01

    Because hepatic glycogenolysis maintains euglycemia during early fasting, proper hepatic glycogen synthesis in the fed/postprandial states is critical. It has been known for decades that gluconeogenesis is essential for hepatic glycogen synthesis; however, the molecular mechanism remains unknown. In this report, we show that depletion of hepatic p300 reduces glycogen synthesis, decreases hepatic glycogen storage, and leads to relative hypoglycemia. We previously reported that insulin suppressed gluconeogenesis by phosphorylating cAMP response element binding protein-binding protein (CBP) at S436 and disassembling the cAMP response element-binding protein-CBP complex. However, p300, which is closely related to CBP, lacks the corresponding S436 phosphorylation site found on CBP. In a phosphorylation-competent p300G422S knock-in mouse model, we found that mutant mice exhibited reduced hepatic glycogen content and produced significantly less glycogen in a tracer incorporation assay in the postprandial state. Our study demonstrates the important and unique role of p300 in glycogen synthesis through maintaining basal gluconeogenesis. PMID:23770612

  20. Long-term survival of women with basal-like ductal carcinoma in situ of the breast: a population-based cohort study

    International Nuclear Information System (INIS)

    Zhou, Wenjing; Jirström, Karin; Johansson, Christine; Amini, Rose-Marie; Blomqvist, Carl; Agbaje, Olorunsola; Wärnberg, Fredrik

    2010-01-01

    Microarray gene-profiling of invasive breast cancer has identified different subtypes including luminal A, luminal B, HER2-overexpressing and basal-like groups. Basal-like invasive breast cancer is associated with a worse prognosis. However, the prognosis of basal-like ductal carcinoma in situ (DCIS) is still unknown. Our aim was to study the prognosis of basal-like DCIS in a large population-based cohort. All 458 women with a primary DCIS diagnosed between 1986 and 2004, in Uppland and Västmanland, Sweden were included. TMA blocks were constructed. To classify the DCIS tumors, we used immunohistochemical (IHC) markers (estrogen-, progesterone-, HER2, cytokeratin 5/6 and epidermal growth factor receptor) as a surrogate for the gene expression profiling. The association with prognosis was examined for basal-like DCIS and other subtypes using Kaplan-Meier survival analyses and Cox proportional hazards regression models. IHC data were complete for 392 women. Thirty-two were basal-like (8.2%), 351 were luminal or HER2-positive (89.5%) and 9 unclassified (2.3%). Seventy-six women had a local recurrence of which 34 were invasive. Another 3 women had general metastases as first event. Basal-like DCIS showed a higher risk of local recurrence and invasive recurrence 1.8 (Confidence interval (CI) 95%, 0.8-4.2) and 1.9 (0.7-5.1), respectively. However, the difference was not statistically significant. Also, no statistically significant increased risk was seen for triple-negative or high grade DCIS. Basal-like DCIS showed about a doubled, however not statistically significant risk for local recurrence and developing invasive cancer compared with the other molecular subtypes. Molecular subtyping was a better prognostic parameter than histopathological grade

  1. DNA endoreduplication, RNA and protein synthesis during growth and development of the antheridial basal cell in Chara vulgaris L

    International Nuclear Information System (INIS)

    Malinowski, S.; Maszewski, J.

    1994-01-01

    Cytophotometric measurements of nuclear DNA contents and morphometric analyses indicate that the level of endo polyploidy plays an important role in determining the maximum size, transcriptional and translational activity that the antheridial basal cell attains during successive stages of spermatogenesis in Chara vulgaris. During the proliferative period of antheridial development, the metabolic activity of basal cell, expressed as the total incorporation of radioactive uridine and leucine was found to increase gradually with the increasing DNA C-values, yet both the synthesis of RNA and then the synthesis of proteins become reduced at the stage preceding spermiogenesis. In accordance with some earlier data, the obtained results seem to support the hypothesis that regulatory mechanisms of symplasmic connections between the antheridium and a thallus participate in the regulation of morphogenesis of the male sex organs in Chara. (author). 15 refs, 13 figs

  2. Cerebral blood flow and metabolism in patients with aphasia due to basal ganglionic lesion

    Energy Technology Data Exchange (ETDEWEB)

    Kitamura, Shin; Kato, Toshiaki; Ujike, Takashi; Kuroki, Soemu; Terashi, Akiro

    1987-03-01

    Cerebral blood flow and metabolism in right handed eight patients with subcortical lesion and aphasia were measured to investigate the correlation between aphasia and functional changes in cerebral blood flow (CBF) and cerebral oxygen consumption (CMRO/sub 2/) in the cortex and the basal ganglionic region. All patients had no lesion in the cortex, but in the basal ganglionic region (putamen, caudate nucleus, internal capsule, and periventricular white matter) on CT images. Patients with bilateral lesion were excluded in this study. Six patients with cerebral infarction in the left basal ganglionic region and two patients with the left putammal hemorrhage were examined. Five patients had non fluent Broca's type speech, two patients had poor comprehension, fluent Wernicke-type speech and one patient was globally aphasic. CBF, CMRO/sub 2/, and oxygen extraction fraction were measured by the positron emission tomography using /sup 15/O/sub 2/, C/sup 15/O/sub 2/ inhalation technique. In addition to reduction of CBF and CMRO/sub 2/ in the basal ganglionic region, CBF and CMRO/sub 2/ decreased in the left frontal cortex especially posterior part in four patients with Broca's aphasia. In two patients with Wernicke type aphasia, CBF and CMRO/sub 2/ decreased in the basal ganglionic region and the left temporal cortex. In a globally aphasic patient, marked reduction of CBF and CMRO/sub 2/ was observed in the left frontal and temporal cortex, in addition to the basal ganglionic region. These results suggest that dysfunction of cortex as well as that of basal ganglionic region might be related to the occurence of aphasia. However, in one patient with Broca's ahasia, CBF and CMRO/sub 2/ were preserved in the cortex and metabolic reduction was observed in only basal ganglia. This case indicates the relation between basal ganglionic lesion and the occurrence of aphasia.

  3. Crossed cerebellar and cerebral cortical diaschisis in basal ganglia hemorrhage

    International Nuclear Information System (INIS)

    Lim, Joon Seok; Ryu, Young Hoon; Kim, Hee Joung; Kim, Byung Moon; Lee, Jong Doo; Lee, Byung Hee

    1998-01-01

    The purpose of this study was to evaluate the phenomenon of diaschisis in the cerebellum and cerebral cortex in patients with pure basal ganglia hemorrhage using cerebral blood flow SPECT. Twelve patients with pure basal ganglia hemorrhage were studied with Tc-99m ECD brain SPECT. Asymmetric index (AI) was calculated in the cerebellum and cerebral cortical regions as | C R -C L |/ (C R -C L ) x 200, where C R and C L are the mean reconstructed counts for the right and left ROIs, respectively. Hypoperfusion was considered to be present when AI was greater than mean + 2 SD of 20 control subjects. Mean AI of the cerebellum and cerebral cortical regions in patients with pure basal ganglia hemorrhage was significantly higher than normal controls (p<0.05): Cerebellum (18.68±8.94 vs 4.35±0.94, mean ±SD), thalamus (31.91±10.61 vs 2.57±1.45), basal ganglia (35.94±16.15 vs 4.34±2.08), parietal (18.94±10.69 vs 3.24±0.87), frontal (13.60±10.8 vs 4.02±2.04) and temporal cortex (18.92±11.95 vs 5.13±1.69). Ten of the 12 patients had significant hypoperfusion in the contralateral cerebellum. Hypoperfusion was also shown in the ipsilateral thalamus (n=12), ipsilateral parietal (n=12), frontal (n=6) and temporal cortex (n=10). Crossed cerebellar diaschisis (CCD) and cortical diaschisis may frequently occur in patients with pure basal ganglia hemorrhage, suggesting that CCD can develop without the interruption of corticopontocerebellar pathway

  4. Mean-field modeling of the basal ganglia-thalamocortical system. II Dynamics of parkinsonian oscillations.

    Science.gov (United States)

    van Albada, S J; Gray, R T; Drysdale, P M; Robinson, P A

    2009-04-21

    Neuronal correlates of Parkinson's disease (PD) include a shift to lower frequencies in the electroencephalogram (EEG) and enhanced synchronized oscillations at 3-7 and 7-30 Hz in the basal ganglia, thalamus, and cortex. This study describes the dynamics of a recent physiologically based mean-field model of the basal ganglia-thalamocortical system, and shows how it accounts for many key electrophysiological correlates of PD. Its detailed functional connectivity comprises partially segregated direct and indirect pathways through two populations of striatal neurons, a hyperdirect pathway involving a corticosubthalamic projection, thalamostriatal feedback, and local inhibition in striatum and external pallidum (GPe). In a companion paper, realistic steady-state firing rates were obtained for the healthy state, and after dopamine loss modeled by weaker direct and stronger indirect pathways, reduced intrapallidal inhibition, lower firing thresholds of the GPe and subthalamic nucleus (STN), a stronger projection from striatum to GPe, and weaker cortical interactions. Here it is shown that oscillations around 5 and 20 Hz can arise with a strong indirect pathway, which also causes increased synchronization throughout the basal ganglia. Furthermore, increased theta power with progressive nigrostriatal degeneration is correlated with reduced alpha power and peak frequency, in agreement with empirical results. Unlike the hyperdirect pathway, the indirect pathway sustains oscillations with phase relationships that coincide with those found experimentally. Alterations in the responses of basal ganglia to transient stimuli accord with experimental observations. Reduced cortical gains due to both nigrostriatal and mesocortical dopamine loss lead to slower changes in cortical activity and may be related to bradykinesia. Finally, increased EEG power found in some studies may be partly explained by a lower effective GPe firing threshold, reduced GPe-GPe inhibition, and/or weaker

  5. Effects of aging on basal fat oxidation in obese humans

    DEFF Research Database (Denmark)

    Solomon, Thomas; Marchetti, Christine M; Krishnan, Raj K

    2008-01-01

    )max) were measured in 10 older (age, 60 +/- 4 years; mean +/- SEM) and 10 younger (age, 35 +/- 4 years) body mass index-matched, obese, normal glucose-tolerant individuals. Fasting blood samples were also collected. Older subjects had slightly elevated fat mass (32.2 +/- 7.1 vs 36.5 +/- 6.7 kg, P......Basal fat oxidation decreases with age. In obesity, it is not known whether this age-related process occurs independently of changes in body composition and insulin sensitivity. Therefore, body composition, resting energy expenditure, basal substrate oxidation, and maximal oxygen consumption (VO(2...... is responsible for reduced basal fat oxidation and maximal oxidative capacity in older obese individuals, independent of changes in insulin resistance, body mass, and abdominal fat. This indicates that age, in addition to obesity, is an independent risk factor for weight gain and for the metabolic complications...

  6. Time representation in reinforcement learning models of the basal ganglia

    Directory of Open Access Journals (Sweden)

    Samuel Joseph Gershman

    2014-01-01

    Full Text Available Reinforcement learning models have been influential in understanding many aspects of basal ganglia function, from reward prediction to action selection. Time plays an important role in these models, but there is still no theoretical consensus about what kind of time representation is used by the basal ganglia. We review several theoretical accounts and their supporting evidence. We then discuss the relationship between reinforcement learning models and the timing mechanisms that have been attributed to the basal ganglia. We hypothesize that a single computational system may underlie both reinforcement learning and interval timing—the perception of duration in the range of seconds to hours. This hypothesis, which extends earlier models by incorporating a time-sensitive action selection mechanism, may have important implications for understanding disorders like Parkinson's disease in which both decision making and timing are impaired.

  7. Single-photon-emission-computed-tomography (SPECT) in basal ganglia disorders

    International Nuclear Information System (INIS)

    Tatsch, K.

    1997-01-01

    In the past, SPECT investigations of regional cerebral blood flow have played a minor role in the diagnostic work-up of patients with basal ganglia disorders. More recently, however, interest in nuclear medicine procedures has dramatically increased since with the development of selective receptor ligands diagnostic tools have been provided which address the pathology in basal ganglia disorders more specifically than other diagnostic modalities. Evaluations of the pre- and postsynaptic aspects of the dopaminergic system, for example, deliver not only interesting data from the scientific point of view but also for the daily routine work. This paper summarizes some of the experience reported in the literature on SPECT investigations in basal ganglia disorders, such as Parkinson's disease, parkinsonian syndromes of other etiology, Wilson's and Huntington's disease, focal dystonias, and schizophrenia under treatment with neuroleptics. (orig.) [de

  8. Selective Vulnerability of the Cochlear Basal Turn to Acrylonitrile and Noise

    International Nuclear Information System (INIS)

    Pouyatos, B.; Gearhart, C.A.; Miller, A.N.; Fulton, S.; Fechter, L.D.; Pouyatos, B.

    2009-01-01

    Exposure to acrylonitrile, a high-production industrial chemical, can promote noise-induced hearing loss (NIHL) in the rat even though this agent does not itself produce permanent hearing loss. The mechanism by which acrylonitrile promotes NIHL includes oxidative stress as antioxidant drugs can partially protect the cochlea from acrylonitrile + noise. Acrylonitrile depletes glutathione levels while noise can increase the formation of reactive oxygen species. It was previously noted that the high-frequency or basal turn of the cochlea was particularly vulnerable to the combined effects of acrylonitrile and noise when the octave band noise (OBN) was centered at 8 k Hz. Normally, such a noise would be expected to yield damage at a more apical region of the cochlea. The present study was designed to determine whether the basal cochlea is selectively sensitive to acrylonitrile or whether, by adjusting the frequency of the noise band, it would be possible to control the region of the auditory impairment. Rats were exposed to one of three different OBNs centered at different frequencies (4 k Hz, 110 dB and 8 or 16 k Hz at 97 dB) for 5 days, with and without administration of acrylonitrile (50 mg/kg/day). The noise was set to cause limited NIHL by itself. Auditory function was monitored by recording distortion products, by compound action potentials, and by performing cochlear histology. While the ACN-only and noise-only exposures induced no or little permanent auditory loss, the three exposures to acrylonitrile + noise produced similar auditory and cochlear impairments above 16 k Hz, despite the fact that the noise exposures covered 2 octaves. These observations show that the basal cochlea is much more sensitive to acrylonitrile + noise than the apical partition. They provide an initial basis for distinguishing the pattern of cochlear injury that results from noise exposure from that which occurs due to the combined effects of noise and a chemical contaminant.

  9. Association of basal serum testosterone levels with ovarian response and in vitro fertilization outcome

    Directory of Open Access Journals (Sweden)

    Sun Mei

    2011-01-01

    Full Text Available Abstract Background To evaluate basal testosterone (T levels during follicular phase of the menstrual cycle as a predictor for ovarian response and in vitro fertilization (IVF outcome. Method We analyzed data retrospectively from hospital-based IVF center including one thousand two hundred and sixty Chinese Han women under their first IVF cycle reached the ovum pick-up stage, without polycystic ovary syndrome (PCOS or endometriosis undergoing long IVF protocol. Patients were divided into 2 groups. Group 1: patients with diminished ovarian reserve (basal FSH >10 IU/L (n = 187; Group 2: patients with normal ovarian reserve (basal FSH Results Basal T levels were markly different between pregnant and non-pregnant women in Group 1; whereas not in Group 2. A testosterone level of 47.85 ng/dl was shown to predict pregnancy outcome with a sensitivity of 52.8% and specificity of 65.3%; and the basal T was correlated with the numbers of large follicles (> 14 mm on HCG day in Group 1. Significantly negative correlations were observed between basal T, days of stimulation and total dose of gonadotropins after adjusting for confounding factors in both groups. Conclusion In women with diminished ovarian reserve, basal T level was a predictor for the number of large follicles on HCG day and pregnancy outcome; but could not in those with normal serum FSH. Basal T levels were associated with both days of stimulation and total dose of gonadotropins, indicating that lower level of T might relate with potential ovarian poor response.

  10. Neglected basal cell carcinoma on scalp

    Directory of Open Access Journals (Sweden)

    Sudip Sarkar

    2016-01-01

    Full Text Available Giant basal cell carcinoma (BCC is a very rare entity. Usually, they occur due to the negligence of the patient. Local or distant metastasis is present in most cases. Here, we present a case of giant BCC that clinically resembled squamous cell carcinoma and demonstrated no metastasis at presentation.

  11. The Arabidopsis DREB2 genetic pathway is constitutively repressed by basal phosphoinositide-dependent phospholipase C coupled to diacylglycerol kinase in Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Nabila eDjafi

    2013-08-01

    Full Text Available Phosphoinositide-dependent phospholipases C (PI-PLCs are activated in response to various stimuli. They utilize substrates provided by type III-Phosphatidylinositol-4 kinases (PI4KIII to produce inositol triphosphate and diacylglycerol (DAG that is phosphorylated into phosphatidic acid (PA by DAG-kinases (DGKs. The roles of PI4KIIIs, PI-PLCs and DGKs in basal signalling are poorly understood. We investigated the control of gene expression by basal PI-PLC pathway in Arabidopsis thaliana suspension cells. A transcriptome-wide analysis allowed the identification of genes whose expression was altered by edelfosine, 30 µM wortmannin or R59022, inhibitors of PI-PLCs, PI4KIIIs and DGKs, respectively. We found that a gene responsive to one of these molecules is more likely to be similarly regulated by the other two inhibitors. The common action of these agents is to inhibit PA formation, showing that basal PI-PLCs act, in part, on gene expression through their coupling to DGKs. Amongst the genes up-regulated in presence of the inhibitors, were some DREB2 genes, in suspension cells and in seedlings. The DREB2 genes encode transcription factors with major roles in responses to environmental stresses, including dehydration. They bind to C-repeat motifs, known as Drought-Responsive Elements, that are indeed enriched in the promoters of genes up-regulated by PI-PLC pathway inhibitors. PA can also be produced by phospholipases D (PLDs. We show that the DREB2 genes that are up-regulated by PI-PLC inhibitors are positively or negatively regulated, or indifferent, to PLD basal activity. Our data show that the DREB2 genetic pathway is constitutively repressed in resting conditions and that DGK coupled to PI-PLC is active in this process, in suspension cells and seedlings. We discuss how this basal negative regulation of DREB2 genes is compatible with their stress-triggered positive regulation.

  12. Crystallization of a compositionally stratified basal magma ocean

    Science.gov (United States)

    Laneuville, Matthieu; Hernlund, John; Labrosse, Stéphane; Guttenberg, Nicholas

    2018-03-01

    Earth's ∼3.45 billion year old magnetic field is regenerated by dynamo action in its convecting liquid metal outer core. However, convection induces an isentropic thermal gradient which, coupled with a high core thermal conductivity, results in rapid conducted heat loss. In the absence of implausibly high radioactivity or alternate sources of motion to drive the geodynamo, the Earth's early core had to be significantly hotter than the melting point of the lower mantle. While the existence of a dense convecting basal magma ocean (BMO) has been proposed to account for high early core temperatures, the requisite physical and chemical properties for a BMO remain controversial. Here we relax the assumption of a well-mixed convecting BMO and instead consider a BMO that is initially gravitationally stratified owing to processes such as mixing between metals and silicates at high temperatures in the core-mantle boundary region during Earth's accretion. Using coupled models of crystallization and heat transfer through a stratified BMO, we show that very high temperatures could have been trapped inside the early core, sequestering enough heat energy to run an ancient geodynamo on cooling power alone.

  13. Dopamine Induces LTP Differentially in Apical and Basal Dendrites through BDNF and Voltage-Dependent Calcium Channels

    Science.gov (United States)

    Navakkode, Sheeja; Sajikumar, Sreedharan; Korte, Martin; Soong, Tuck Wah

    2012-01-01

    The dopaminergic modulation of long-term potentiation (LTP) has been studied well, but the mechanism by which dopamine induces LTP (DA-LTP) in CA1 pyramidal neurons is unknown. Here, we report that DA-LTP in basal dendrites is dependent while in apical dendrites it is independent of activation of L-type voltage-gated calcium channels (VDCC).…

  14. A novel method of basal crevasse height estimation and subsequent rifting

    Science.gov (United States)

    Logan, L.; Catania, G. A.; Lavier, L. L.; Choi, E.

    2012-12-01

    Basal crevasses may play an important precursory role in the location and propagation of rifts and in ice shelf disintegration. Here we develop a novel method for estimating the locations and heights of basal crevasses formed at the grounding line of ice shelves and ice streams. We assume a thin-elastic beam formulation (TEB) with a tensional plastic yielding criterion to capture the physics of a tidally flexed grounding line. Observations of basal crevasses in the Siple Coast area match well with predictions produced by this method. Areas with large misfit can be delineated by examining the strain rate field; indeed, in our estimations those crevasses which deviate most from the TEB prediction lie directly in a shear margin. We test the method against other areas in the Larsen Ice Shelf, and find again a good match. Thus we suggest the TEB as an alternative to other crevasse estimation methods, as it produces a good fit in predominantly tensile regions, requires no tuning or prior information, and is computationally free to implement into large scale ice models which aim at physically simulating calving and fracture processes. We pursue modeling basal crevasses as they evolve with a thermomechanical finite-difference 3-dimensional model called SNAC. Viscoelastoplastic ice follows Mohr-Coulomb tension failure with Glen's flow law. We examine the conditions necessary for a basal crevasse formed on the downstream side of an ice rise to propagate the full thickness of the ice, developing into a rift.

  15. Aberrant functional connectivity within the basal ganglia of patients with Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Michal Rolinski

    2015-01-01

    Full Text Available Resting state functional MRI (rs-fMRI has been previously shown to be a promising tool for the assessment of early Parkinson's disease (PD. In order to assess whether changes within the basal ganglia network (BGN are disease specific or relate to neurodegeneration generally, BGN connectivity was assessed in 32 patients with early PD, 19 healthy controls and 31 patients with Alzheimer's disease (AD. Voxel-wise comparisons demonstrated decreased connectivity within the basal ganglia of patients with PD, when compared to patients with AD and healthy controls. No significant changes within the BGN were seen in AD, when compared to healthy controls. Moreover, measures of functional connectivity extracted from regions within the basal ganglia were significantly lower in the PD group. Consistent with previous radiotracer studies, the greatest change when compared to the healthy control group was seen in the posterior putamen of PD subjects. When combined into a single component score, this method differentiated PD from AD and healthy control subjects, with a diagnostic accuracy of 81%. Rs-fMRI can be used to demonstrate the aberrant functional connectivity within the basal ganglia of patients with early PD. These changes are likely to be representative of patho-physiological basal ganglia dysfunction and are not associated with generalised neurodegeneration seen in AD. Further studies are necessary to ascertain whether this method is sensitive enough to detect basal ganglia dysfunction in prodromal PD, and its utility as a potential diagnostic biomarker for premotor and early motoric disease.

  16. Sequence of cDNAs for mammalian H2A. Z, an evolutionarily diverged but highly conserved basal histone H2A isoprotein species

    Energy Technology Data Exchange (ETDEWEB)

    Hatch, C L; Bonner, W M

    1988-02-11

    The nucleotide sequences of cDNAs for the evolutionarily diverged but highly conserved basal H2A isoprotein, H2A.Z, have been determined for the rat, cow, and human. As a basal histone, H2A.Z is synthesized throughout the cell cycle at a constant rate, unlinked to DNA replication, and at a much lower rate in quiescent cells. Each of the cDNA isolates encodes the entire H2A.Z polypeptide. The human isolate is about 1.0 kilobases long. It contains a coding region of 387 nucleotides flanked by 106 nucleotides of 5'UTR and 376 nucleotides of 3'UTR, which contains a polyadenylation signal followed by a poly A tail. The bovine and rat cDNAs have 97 and 94% nucleotide positional identity to the human cDNA in the coding region and 98% in the proximal 376 nucleotides of the 3'UTR which includes the polyadenylation signal. A potential stem-forming sequence imbedded in a direct repeat is found centered at 261 nucleotides into the 3'UTR. Each of the cDNA clones could be transcribed and translated in vitro to yield H2A.Z protein. The mammalian H2A.Z cDNA coding sequences are approximately 80% similar to those in chicken and 75% to those in sea urchin.

  17. Phenotypic spectrum of probable and genetically-confirmed idiopathic basal ganglia calcification.

    Science.gov (United States)

    Nicolas, Gaël; Pottier, Cyril; Charbonnier, Camille; Guyant-Maréchal, Lucie; Le Ber, Isabelle; Pariente, Jérémie; Labauge, Pierre; Ayrignac, Xavier; Defebvre, Luc; Maltête, David; Martinaud, Olivier; Lefaucheur, Romain; Guillin, Olivier; Wallon, David; Chaumette, Boris; Rondepierre, Philippe; Derache, Nathalie; Fromager, Guillaume; Schaeffer, Stéphane; Krystkowiak, Pierre; Verny, Christophe; Jurici, Snejana; Sauvée, Mathilde; Vérin, Marc; Lebouvier, Thibaud; Rouaud, Olivier; Thauvin-Robinet, Christel; Rousseau, Stéphane; Rovelet-Lecrux, Anne; Frebourg, Thierry; Campion, Dominique; Hannequin, Didier

    2013-11-01

    Idiopathic basal ganglia calcification is characterized by mineral deposits in the brain, an autosomal dominant pattern of inheritance in most cases and genetic heterogeneity. The first causal genes, SLC20A2 and PDGFRB, have recently been reported. Diagnosing idiopathic basal ganglia calcification necessitates the exclusion of other causes, including calcification related to normal ageing, for which no normative data exist. Our objectives were to diagnose accurately and then describe the clinical and radiological characteristics of idiopathic basal ganglia calcification. First, calcifications were evaluated using a visual rating scale on the computerized tomography scans of 600 consecutively hospitalized unselected controls. We determined an age-specific threshold in these control computerized tomography scans as the value of the 99th percentile of the total calcification score within three age categories: 60 years. To study the phenotype of the disease, patients with basal ganglia calcification were recruited from several medical centres. Calcifications that rated below the age-specific threshold using the same scale were excluded, as were patients with differential diagnoses of idiopathic basal ganglia calcification, after an extensive aetiological assessment. Sanger sequencing of SLC20A2 and PDGFRB was performed. In total, 72 patients were diagnosed with idiopathic basal ganglia calcification, 25 of whom bore a mutation in either SLC20A2 (two families, four sporadic cases) or PDGFRB (one family, two sporadic cases). Five mutations were novel. Seventy-one per cent of the patients with idiopathic basal ganglia calcification were symptomatic (mean age of clinical onset: 39 ± 20 years; mean age at last evaluation: 55 ± 19 years). Among them, the most frequent signs were: cognitive impairment (58.8%), psychiatric symptoms (56.9%) and movement disorders (54.9%). Few clinical differences appeared between SLC20A2 and PDGFRB mutation carriers. Radiological analysis

  18. Influence of basal application of organic wastes on absorption and translocation of 15N-tagged nitrogen fertilizer in tea plants

    International Nuclear Information System (INIS)

    Watanabe, Ikuo; Ikegaya, Kenjiro; Hiramine, Shigeo

    1979-01-01

    Influence of the basal application of rape seed oil cake and shavings pig manure compost on the absorption, translocation and utilization of top-dressed 15 N-tagged ammonium sulfate in tea plants were studied. Nitrogen uptake and dry weights of new shoots increased in rape seed oil cake and shavings pig manure compost treatments as compared with ammonium sulfate treatments. The high rate of nitrogen absorption per the weight of rootlets in rape seed oil cake treatments suggested that the enhanced root activity might contribute to the increase. And the increase in shavings pig manure compost treatments could be due to the increase of the quantity of rootlets. The absorbed tagged nitrogen was 34% of total absorbed nitrogen in rape seed oil cake treatments, and 67% in shavings pig manure treatments. The results suggested that available nitrogen contents in soil originated from the basal nitrogen might be low in shavings pig manure compost treatments in comparison with rape seed oil cake treatments. Total nitrogen and nitrogen contents of amino acid fraction of ''a bud and two leaves'' of new shoots were relatively high in shavings pig manure compost treatments. With the growth of new shoots, nitrogen contents of protein fraction decreased in old leaves, branches and trunks in ammonium sulfate and rape seed oil cake treatments. This fact suggested that the storage protein might be present in these organs. (author)

  19. Synergy as a new and sensitive marker of basal ganglia dysfunction: A study of asymptomatic welders.

    Science.gov (United States)

    Lewis, Mechelle M; Lee, Eun-Young; Jo, Hang Jin; Du, Guangwei; Park, Jaebum; Flynn, Michael R; Kong, Lan; Latash, Mark L; Huang, Xuemei

    2016-09-01

    Multi-digit synergies, a recently developed, theory-based method to quantify stability of motor action, are shown to reflect basal ganglia dysfunction associated with parkinsonian syndromes. In this study, we tested the hypothesis that multi-digit synergies may capture early and subclinical basal ganglia dysfunction. We chose asymptomatic welders to test the hypothesis because the basal ganglia are known to be most susceptible to neurotoxicity caused by welding-related metal accumulation (such as manganese and iron). Twenty right-handed welders and 13 matched controls were invited to perform single- and multi-finger pressing tasks using the fingers of the right or left hand. Unified Parkinson's Disease Rating Scale and Grooved Pegboard scores were used to gauge gross and fine motor dysfunction, respectively. High-resolution (3T) T1-weighted, T2-weighted, T1 mapping, susceptibility, and diffusion tensor MRIs were obtained to reflect manganese, iron accumulation, and microstructural changes in basal ganglia. The synergy index stabilizing total force and anticipatory synergy adjustments were computed, compared between groups, and correlated with estimates of basal ganglia manganese [the pallidal index, R1 (1/T1)], iron [R2* (1/T2*)], and microstructural changes [fractional anisotropy and mean diffusivity]. There were no significant differences in Unified Parkinson's Disease Rating Scale (total or motor subscale) or Grooved Pegboard test scores between welders and controls. The synergy index during steady-state accurate force production was decreased significantly in the left hand of welders compared to controls (p=0.004) but did not reach statistical significance in the right hand (p=0.16). Anticipatory synergy adjustments, however, were not significantly different between groups. Among welders, higher synergy indices in the left hand were associated significantly with higher fractional anisotropy values in the left globus pallidus (R=0.731, psynergy metrics may serve

  20. Late Cambrian magmatic arc activity in peri-Gondwana: geochemical evidence from the Basal Allochthonous Units of NW Iberia

    Energy Technology Data Exchange (ETDEWEB)

    Andonaegui, P.; Abati, J.; Díez-Fernández, R.

    2017-07-01

    The North African section of the Gondwana margin was the site of voluminous, arc-related magmatism during the Late Neoproterozoic (Avalonian–Cadomian orogen). The lower (and older) metasedimentary sequence that constitutes the Basal Units of the Allochthonous Complexes of NW Iberia was deposited in that setting. In these units, sedimentation was followed by the intrusion of tonalites and granodiorites in the late Cambrian (ca. 493–489Ma). In the Late Paleozoic, the collision of Gondwana and Laurussia (Variscan orogeny) deformed and metamorphosed the whole ensemble. New whole rock geochemical analysis performed in seven samples of metatonalites and fourteen samples of metagranodiorites are characterized by: i) slight enrichment in incompatible elements (Rb, Ba, Th, U), ii) negative anomalies in Nb, Ta, P, and Ti, and iii) negative anomalies in Eu. These chemical features are in agreement with a subduction-related setting for the genesis of both types of magma, which is also supported by chemical discrimination using tectonic setting diagrams. Positive anomalies of Pb suggest a crustal component. The new geochemical data reveal that the convergent orogen that ruled the paleogeography of the Gondwana periphery during the Neoproterozoic (Cadomian orogen) remained active bey.

  1. Basal-topographic control of stationary ponds on a continuously moving landslide

    Science.gov (United States)

    Coe, J.A.; McKenna, J.P.; Godt, J.W.; Baum, R.L.

    2009-01-01

    The Slumgullion landslide in the San Juan Mountains of southwestern Colorado has been moving for at least the last few hundred years and has multiple ponds on its surface. We have studied eight ponds during 30 trips to the landslide between July 1998 and July 2007. During each trip, we have made observations on the variability in pond locations and water levels, taken ground-based photographs to document pond water with respect to moving landslide material and vegetation, conducted Global Positioning System surveys of the elevations of water levels and mapped pond sediments on the landslide surface. Additionally, we have used stereo aerial photographs taken in October 1939, October 1940 and July 2000 to measure topographic profiles of the eight pond locations, as well as a longitudinal profile along the approximate centerline of the landslide, to examine topographic changes over a 60- to 61-year period of time. Results from field observations, analyses of photographs, mapping and measurements indicate that all pond locations have remained spatially stationary for 60-300 years while landslide material moves through these locations. Water levels during the observation period were sensitive to changes in the local, spring-fed, stream network, and to periodic filling of pond locations by sediment from floods, hyperconcentrated flows, mud flows and debris flows. For pond locations to remain stationary, the locations must mimic depressions along the basal surface of the landslide. The existence of such depressions indicates that the topography of the basal landslide surface is irregular. These results suggest that, for translational landslides that have moved distances larger than the dimensions of the largest basal topographic irregularities (about 200 m at Slumgullion), landslide surface morphology can be used as a guide to the morphology of the basal slip surface. Because basal slip surface morphology can affect landslide stability, kinematic models and stability

  2. Impact of basal diet on dextran sodium sulphate (DSS)-induced colitis in rats.

    Science.gov (United States)

    Boussenna, Ahlem; Goncalves-Mendes, Nicolas; Joubert-Zakeyh, Juliette; Pereira, Bruno; Fraisse, Didier; Vasson, Marie-Paule; Texier, Odile; Felgines, Catherine

    2015-12-01

    Dextran sodium sulphate (DSS)-induced colitis is a widely used model for inflammatory bowel disease. However, various factors including nutrition may affect the development of this colitis. This study aimed to compare and characterize the impact of purified and non-purified basal diets on the development of DSS-induced colitis in the rat. Wistar rats were fed a non-purified or a semi-synthetic purified diet for 21 days. Colitis was then induced in half of the rats by administration of DSS in drinking water (4% w/v) during the last 7 days of experimentation. At the end of the experimental period, colon sections were taken for histopathological examination, determination of various markers of inflammation (myeloperoxidase: MPO, cytokines) and oxidative stress (superoxide dismutase: SOD, catalase: CAT, glutathione peroxidase: GPx and glutathione reductase: GRed activities), and evaluation of the expression of various genes implicated in this disorder. DSS ingestion induced a more marked colitis in animals receiving the purified diet, as reflected by higher histological score and increased MPO activity. A significant decrease in SOD and CAT activities was also observed in rats fed the purified diet. Also, in these animals, administration of DSS induced a significant increase in interleukin (IL)-1α, IL-1β and IL-6. In addition, various genes implicated in inflammation were over-expressed after ingestion of DSS by rats fed the purified diet. These results show that a purified diet promotes the onset of a more severe induced colitis than a non-purified one, highlighting the influence of basal diet in colitis development.

  3. Association of basal serum androgen levels with ovarian response and ICSI cycle outcome.

    Science.gov (United States)

    Abide Yayla, C; Ozkaya, E; Kayatas Eser, S; Sanverdi, I; Devranoglu, B; Kutlu, T

    2018-05-01

    The purpose of this study was to assess the predictive value of basal serum testosterone (T) and dehydroepiandrosterone sulfate (DHEAS) levels during follicular phase for ovarian response and outcome in intracytoplasmic sperm injection (ICSI) cycles of women with diminished ovarian reserve. We prospectively gathered data of basal serum androgen levels and ICSI cycle characteristics of 120 women with diminished ovarian reserve. Association of basal serum T and DHEAS levels with ovarian response was analyzed. Basal T and DHEAS levels were similar between pregnant and non-pregnant cases (P > 0.05). There were significant differences between groups with and without successful embryo implantation in terms of serum follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), gonadotropin starting and total dose, and peak estradiol level (P stimulation due to unresponsiveness (n = 26, 21.7%), no oocyte at oocyte pickup (n = 11, 9.2%), no mature oocyte (n = 6, 5%), and failure of fertilization or embryo development (n = 15, 12.5%). Basal androgen levels were not significant predictors for any of the cycle outcome. AMH level was a significant predictor for failure of fertilization or embryo development (AUC 0.722, P = 0.01) and cancelation of stimulation (AUC 0.801, P stimulation (AUC 0.774, P basal T and DHEAS levels have no value in predicting any of the cycle outcome parameters.

  4. Patient awareness and sun protection behaviour following excision of basal cell carcinoma.

    Science.gov (United States)

    de Blacam, Catherine; Dermott, Clodagh Mc; Sugrue, Conor; Kilmartin, Darren; Kelly, Jack

    2017-02-01

    Limited information is available regarding disease awareness and sun protection behaviour in patients previously treated for non-melanoma skin cancer. Using a telephone-administered questionnaire, we investigated these characteristics in 250 patients in the west of Ireland who had undergone excision of basal cell carcinomas between January 2011 and December 2012. Only 28.8% of respondents knew that the lesion they had excised was a BCC and understood that there was a significant chance of developing another similar lesion in the next 3 years. Women and patients under age 65 were significantly better informed about their diagnosis than men (p = 0.021 and 0.000 respectively). The majority of patients (71.2%) knew that the overall effect of UV radiation on the skin was harmful and did employ some form of sun protection (avoid midday sun 72%; stay in shade 74%; wear hat 73.6%; wear sunscreen 72.8%). Females were statistically more likely to exercise better sun-protection behaviour (p = 0.002). While 76.8% of patients undertook some form of outdoor activity every day, only 22.8% wore sunscreen every day. Greater efforts should be made to communicate disease details and sun protection implications associated with basal cell carcinoma, especially to male patients. Improved population specific skin cancer awareness may lead to earlier detection and thus decrease both the patient morbidity and economic burden associated with locally advanced basal cell carcinoma. Copyright © 2015 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.

  5. Hypoattenuation of the basal nuclei as a sign of propionic acidemia

    International Nuclear Information System (INIS)

    Asenjo, M.; Moron, A.; Marti, M.; Dominguez, F.

    1999-01-01

    The hypoattenuation of the basal ganglia is an uncommon radiological finding that suggests a metabolic or hypoxic disorder. We report a case of propionic acidemia in a five-year-old boy, presenting as a symmetric hypoattenuation of the basal neclei. We discuss this and other causes of this radiological finding, as well as the possible mechanism and underlying pathology. (Author) 17 refs

  6. Multiple jaw cysts not associated with basal cell nevus syndrome

    International Nuclear Information System (INIS)

    Yoon, Suk Ja; Kang, Byung Cheol

    2003-01-01

    We present two cases of multiple jaw cysts not associated with basal cell nevus syndrome. Case 1 : a nine year-old boy visited CNU Hospital for orthodontic treatment and his radiographs showed cystic lesions surrounding the crowns of teeth 13 and 17 respectively, which were diagnosed as dentigerous cysts. Subsequently, two more cysts were found on his follow-up radiographs in 12 and 15 months. The two cysts were determined to be odontogenic keratocysts. The boy had no skeletal abnormalities and no skin lesions associated with basal cell nevus syndrome. Case 2: a fifty-eight year old man had three impacted third molars with pericoronal radiolucencies, which were diagnosed as dentigerous cysts. He had no additional abnormalities associated with basal cell nevus syndrome. Multiple jaw cysts can occur at any age, and periodic radiographic surveillance may be needed for any cases of impacted tooth.

  7. Multiple jaw cysts not associated with basal cell nevus syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Suk Ja; Kang, Byung Cheol [Chonnam National University College of Medicine, Kwangju (Korea, Republic of)

    2003-09-15

    We present two cases of multiple jaw cysts not associated with basal cell nevus syndrome. Case 1 : a nine year-old boy visited CNU Hospital for orthodontic treatment and his radiographs showed cystic lesions surrounding the crowns of teeth 13 and 17 respectively, which were diagnosed as dentigerous cysts. Subsequently, two more cysts were found on his follow-up radiographs in 12 and 15 months. The two cysts were determined to be odontogenic keratocysts. The boy had no skeletal abnormalities and no skin lesions associated with basal cell nevus syndrome. Case 2: a fifty-eight year old man had three impacted third molars with pericoronal radiolucencies, which were diagnosed as dentigerous cysts. He had no additional abnormalities associated with basal cell nevus syndrome. Multiple jaw cysts can occur at any age, and periodic radiographic surveillance may be needed for any cases of impacted tooth.

  8. Nevoid basal cell carcinoma syndrome with medulloblastoma and meningioma. Case report

    International Nuclear Information System (INIS)

    Fukushima, Yutaka; Oka, Hidehiro; Utsuki, Satoshi; Iwamoto, Kazuhisa; Fujii, Kiyotaka

    2004-01-01

    A 35-year-old man presented with a rare case of nevoid basal cell carcinoma syndrome, or Gorlin's syndrome, associated with both medulloblastoma and meningioma, manifesting as visual field constriction due to multiple parasellar tumors. He had undergone resection of a medulloblastoma at the age of 1 year 9 months, followed by adjunctive irradiation with a total dose of 40 Gy. He presented with multiple subcutaneous nodules on his face and neck. Histological examination of biopsy specimens established the diagnosis of nevoid basal cell carcinoma syndrome. Tuberculum sellae meningioma was removed through a craniotomy, and his symptoms improved. Meningioma is known to occur in the field of therapeutic irradiation, so chemotherapy may be a better option for medulloblastoma associated with nevoid basal cell carcinoma syndrome. (author)

  9. A Biologically Inspired Computational Model of Basal Ganglia in Action Selection.

    Science.gov (United States)

    Baston, Chiara; Ursino, Mauro

    2015-01-01

    The basal ganglia (BG) are a subcortical structure implicated in action selection. The aim of this work is to present a new cognitive neuroscience model of the BG, which aspires to represent a parsimonious balance between simplicity and completeness. The model includes the 3 main pathways operating in the BG circuitry, that is, the direct (Go), indirect (NoGo), and hyperdirect pathways. The main original aspects, compared with previous models, are the use of a two-term Hebb rule to train synapses in the striatum, based exclusively on neuronal activity changes caused by dopamine peaks or dips, and the role of the cholinergic interneurons (affected by dopamine themselves) during learning. Some examples are displayed, concerning a few paradigmatic cases: action selection in basal conditions, action selection in the presence of a strong conflict (where the role of the hyperdirect pathway emerges), synapse changes induced by phasic dopamine, and learning new actions based on a previous history of rewards and punishments. Finally, some simulations show model working in conditions of altered dopamine levels, to illustrate pathological cases (dopamine depletion in parkinsonian subjects or dopamine hypermedication). Due to its parsimonious approach, the model may represent a straightforward tool to analyze BG functionality in behavioral experiments.

  10. A Biologically Inspired Computational Model of Basal Ganglia in Action Selection

    Directory of Open Access Journals (Sweden)

    Chiara Baston

    2015-01-01

    Full Text Available The basal ganglia (BG are a subcortical structure implicated in action selection. The aim of this work is to present a new cognitive neuroscience model of the BG, which aspires to represent a parsimonious balance between simplicity and completeness. The model includes the 3 main pathways operating in the BG circuitry, that is, the direct (Go, indirect (NoGo, and hyperdirect pathways. The main original aspects, compared with previous models, are the use of a two-term Hebb rule to train synapses in the striatum, based exclusively on neuronal activity changes caused by dopamine peaks or dips, and the role of the cholinergic interneurons (affected by dopamine themselves during learning. Some examples are displayed, concerning a few paradigmatic cases: action selection in basal conditions, action selection in the presence of a strong conflict (where the role of the hyperdirect pathway emerges, synapse changes induced by phasic dopamine, and learning new actions based on a previous history of rewards and punishments. Finally, some simulations show model working in conditions of altered dopamine levels, to illustrate pathological cases (dopamine depletion in parkinsonian subjects or dopamine hypermedication. Due to its parsimonious approach, the model may represent a straightforward tool to analyze BG functionality in behavioral experiments.

  11. σ2-Adaptin Facilitates Basal Synaptic Transmission and Is Required for Regenerating Endo-Exo Cycling Pool Under High-Frequency Nerve Stimulation in Drosophila.

    Science.gov (United States)

    Choudhury, Saumitra Dey; Mushtaq, Zeeshan; Reddy-Alla, Suneel; Balakrishnan, Sruthi S; Thakur, Rajan S; Krishnan, Kozhalmannom S; Raghu, Padinjat; Ramaswami, Mani; Kumar, Vimlesh

    2016-05-01

    The functional requirement of adapter protein 2 (AP2) complex in synaptic membrane retrieval by clathrin-mediated endocytosis is not fully understood. Here we isolated and functionally characterized a mutation that dramatically altered synaptic development. Based on the aberrant neuromuscular junction (NMJ) synapse, we named this mutation angur (a Hindi word meaning "grapes"). Loss-of-function alleles of angur show more than twofold overgrowth in bouton numbers and a dramatic decrease in bouton size. We mapped the angur mutation to σ2-adaptin, the smallest subunit of the AP2 complex. Reducing the neuronal level of any of the subunits of the AP2 complex or disrupting AP2 complex assembly in neurons phenocopied the σ2-adaptin mutation. Genetic perturbation of σ2-adaptin in neurons leads to a reversible temperature-sensitive paralysis at 38°. Electrophysiological analysis of the mutants revealed reduced evoked junction potentials and quantal content. Interestingly, high-frequency nerve stimulation caused prolonged synaptic fatigue at the NMJs. The synaptic levels of subunits of the AP2 complex and clathrin, but not other endocytic proteins, were reduced in the mutants. Moreover, bone morphogenetic protein (BMP)/transforming growth factor β (TGFβ) signaling was altered in these mutants and was restored by normalizing σ2-adaptin in neurons. Thus, our data suggest that (1) while σ2-adaptin facilitates synaptic vesicle (SV) recycling for basal synaptic transmission, its activity is also required for regenerating SVs during high-frequency nerve stimulation, and (2) σ2-adaptin regulates NMJ morphology by attenuating TGFβ signaling. Copyright © 2016 by the Genetics Society of America.

  12. The basal forebrain cholinergic system in aging and dementia : Rescuing cholinergic neurons from neurotoxic amyloid-beta 42 with memantine

    NARCIS (Netherlands)

    Nyakas, Csaba; Granic, Ivica; Halmy, Laszlo G.; Banerjee, Pradeep; Luiten, Paul G. M.

    2011-01-01

    The dysfunction and loss of basal forebrain cholinergic neurons and their cortical projections are among the earliest pathological events in the pathogenesis of Alzheimer's disease (AD). The evidence pointing to cholinergic impairments come from studies that report a decline in the activity of

  13. The basal part of the Oman ophiolitic mantle: a fossil Mantle Wedge?

    Science.gov (United States)

    Prigent, Cécile; Guillot, Stéphane; Agard, Philippe; Godard, Marguerite; Chauvet, Alain; Dubacq, Benoit; Monié, Patrick; Yamato, Philippe

    2014-05-01

    Although the Oman ophiolite is classically regarded as being the direct analog of oceanic lithosphere created at fast spreading ridges, the geodynamic context of its formation is still highly debated. The other alternative end-member model suggests that this ophiolite entirely formed in a supra-subduction zone setting. Fluids involved in the hydration of the oceanic lithosphere and in the presence of a secondary boninitic and andesitic volcanism may provide a way to discriminate between these two interpretations: are they descending near-axis hydrothermal fluxes (first model) or ascending from a subducting slab (second model)? We herein focus on the base of the ophiolitic mantle in order to characterize the origin of fluids and decipher hydration processes. Samples were taken along hecto- to kilometre-long sections across the basal banded unit directly overlying the amphibolitic/granulitic metamorphic sole. We carried out a petrological, structural and geochemical study on these rocks and their constitutive minerals. Our results show that, unlike the generally refractory character of Oman harzburgites, all the basal mantle rocks display secondary crystallization of clinopyroxene and amphibole through metasomatic processes. The microstructures and the chronology of these secondary mineralizations (clinopyroxene, pargasitic amphibole, antigorite and then lizardite/chrysotile) suggest that these basal rocks have been affected by cooling from mantle temperatures (serpentines (B, Sr, Rb, Ba, As), are consistent with amphibolite-derived fluids (Ishikawa et al., 2005) and cannot be easily explained by other sources. Based on these observations, we propose a geodynamic model in which intense and continuous metasomatism of the cooling base of the ophiolitic mantle is due to the release of fluids coming from the progressive dehydration of underlying amphibolitic rocks. This process is compatible with the progressive subduction of the Arabian margin during the Upper

  14. Extrahepatic portal vein obstruction with parkinsonism and symmetric hyperintense basal ganglia on T1 weighted MRI

    Directory of Open Access Journals (Sweden)

    Jayalakshmi Sita

    2006-01-01

    Full Text Available Abnormal high signal in the globus pallidus on T1 weighted magnetic resonance imaging (MRI of the brain has been well described in patients with chronic liver disease. It may be related to liver dysfunction or portal-systemic shunting. We report a case of extra hepatic portal vein obstruction with portal hypertension and esophageal varices that presented with extra pyramidal features. T1 weighted MRI brain scans showed increased symmetrical signal intensities in the basal ganglia. Normal hepatic function in this patient emphasizes the role of portal- systemic communications in the development of these hyperintensities, which may be due to deposition of paramagnetic substances like manganese in the basal ganglia.

  15. Cerebral blood flow and metabolism in patients with aphasia due to basal ganglionic lesion

    International Nuclear Information System (INIS)

    Kitamura, Shin; Kato, Toshiaki; Ujike, Takashi; Kuroki, Soemu; Terashi, Akiro

    1987-01-01

    Cerebral blood flow and metabolism in right handed eight patients with subcortical lesion and aphasia were measured to investigate the correlation between aphasia and functional changes in cerebral blood flow (CBF) and cerebral oxygen consumption (CMRO 2 ) in the cortex and the basal ganglionic region. All patients had no lesion in the cortex, but in the basal ganglionic region (putamen, caudate nucleus, internal capsule, and periventricular white matter) on CT images. Patients with bilateral lesion were excluded in this study. Six patients with cerebral infarction in the left basal ganglionic region and two patients with the left putammal hemorrhage were examined. Five patients had non fluent Broca's type speech, two patients had poor comprehension, fluent Wernicke-type speech and one patient was globally aphasic. CBF, CMRO 2 , and oxygen extraction fraction were measured by the positron emission tomography using 15 O 2 , C 15 O 2 inhalation technique. In addition to reduction of CBF and CMRO 2 in the basal ganglionic region, CBF and CMRO 2 decreased in the left frontal cortex especially posterior part in four patients with Broca's aphasia. In two patients with Wernicke type aphasia, CBF and CMRO 2 decreased in the basal ganglionic region and the left temporal cortex. In a globally aphasic patient, marked reduction of CBF and CMRO 2 was observed in the left frontal and temporal cortex, in addition to the basal ganglionic region. These results suggest that dysfunction of cortex as well as that of basal ganglionic region might be related to the occurence of aphasia. However, in one patient with Broca's ahasia, CBF and CMRO 2 were preserved in the cortex and metabolic reduction was observed in only basal ganglia. This case indicates the relation between basal ganglionic lesion and the occurrence of aphasia. These results suggest that measurements of cerebral blood flow and metabolism were necessary to study the responsible lesion for aphasia. (author)

  16. Long-lasting memory deficits in mice withdrawn from cocaine are concomitant with neuroadaptations in hippocampal basal activity, GABAergic interneurons and adult neurogenesis

    Directory of Open Access Journals (Sweden)

    David Ladrón de Guevara-Miranda

    2017-03-01

    Full Text Available Cocaine addiction disorder is notably aggravated by concomitant cognitive and emotional pathology that impedes recovery. We studied whether a persistent cognitive/emotional dysregulation in mice withdrawn from cocaine holds a neurobiological correlate within the hippocampus, a limbic region with a key role in anxiety and memory but that has been scarcely investigated in cocaine addiction research. Mice were submitted to a chronic cocaine (20 mg/kg/day for 12 days or vehicle treatment followed by 44 drug-free days. Some mice were then assessed on a battery of emotional (elevated plus-maze, light/dark box, open field, forced swimming and cognitive (object and place recognition memory, cocaine-induced conditioned place preference, continuous spontaneous alternation behavioral tests, while other mice remained in their home cage. Relevant hippocampal features [basal c-Fos activity, GABA+, parvalbumin (PV+ and neuropeptide Y (NPY+ interneurons and adult neurogenesis (cell proliferation and immature neurons] were immunohistochemically assessed 73 days after the chronic cocaine or vehicle protocol. The cocaine-withdrawn mice showed no remarkable exploratory or emotional alterations but were consistently impaired in all the cognitive tasks. All the cocaine-withdrawn groups, independent of whether they were submitted to behavioral assessment or not, showed enhanced basal c-Fos expression and an increased number of GABA+ cells in the dentate gyrus. Moreover, the cocaine-withdrawn mice previously submitted to behavioral training displayed a blunted experience-dependent regulation of PV+ and NPY+ neurons in the dentate gyrus, and neurogenesis in the hippocampus. Results highlight the importance of hippocampal neuroplasticity for the ingrained cognitive deficits present during chronic cocaine withdrawal.

  17. Learning Reward Uncertainty in the Basal Ganglia.

    Directory of Open Access Journals (Sweden)

    John G Mikhael

    2016-09-01

    Full Text Available Learning the reliability of different sources of rewards is critical for making optimal choices. However, despite the existence of detailed theory describing how the expected reward is learned in the basal ganglia, it is not known how reward uncertainty is estimated in these circuits. This paper presents a class of models that encode both the mean reward and the spread of the rewards, the former in the difference between the synaptic weights of D1 and D2 neurons, and the latter in their sum. In the models, the tendency to seek (or avoid options with variable reward can be controlled by increasing (or decreasing the tonic level of dopamine. The models are consistent with the physiology of and synaptic plasticity in the basal ganglia, they explain the effects of dopaminergic manipulations on choices involving risks, and they make multiple experimental predictions.

  18. Calcineurin Aβ regulates NADPH oxidase (Nox) expression and activity via nuclear factor of activated T cells (NFAT) in response to high glucose.

    Science.gov (United States)

    Williams, Clintoria R; Gooch, Jennifer L

    2014-02-21

    Hypertrophy is an adaptive response that enables organs to appropriately meet increased functional demands. Previously, we reported that calcineurin (Cn) is required for glomerular and whole kidney hypertrophy in diabetic rodents (Gooch, J. L., Barnes, J. L., Garcia, S., and Abboud, H. E. (2003). Calcineurin is activated in diabetes and is required for glomerular hypertrophy and ECM accumulation. Am. J. Physiol. Renal Physiol. 284, F144-F154; Reddy, R. N., Knotts, T. L., Roberts, B. R., Molkentin, J. D., Price, S. R., and Gooch, J. L. (2011). Calcineurin Aβ is required for hypertrophy but not matrix expansion in the diabetic kidney. J. Cell Mol. Med. 15, 414-422). Because studies have also implicated the reactive oxygen species-generating enzymes NADPH oxidases (Nox) in diabetic kidney responses, we tested the hypothesis that Nox and Cn cooperate in a common signaling pathway. First, we examined the role of the two main isoforms of Cn in hypertrophic signaling. Using primary kidney cells lacking a catalytic subunit of Cn (CnAα(-/-) or CnAβ(-/-)), we found that high glucose selectively activates CnAβ, whereas CnAα is constitutively active. Furthermore, CnAβ but not CnAα mediates hypertrophy. Next, we found that chronic reactive oxygen species generation in response to high glucose is attenuated in CnAβ(-/-) cells, suggesting that Cn is upstream of Nox. Consistent with this, loss of CnAβ reduces basal expression and blocks high glucose induction of Nox2 and Nox4. Inhibition of nuclear factor of activated T cells (NFAT), a CnAβ-regulated transcription factor, decreases Nox2 and Nox4 expression, whereas NFAT overexpression increases Nox2 and Nox4, indicating that the CnAβ/NFAT pathway modulates Nox. These data reveal that the CnAβ/NFAT pathway regulates Nox and plays an important role in high glucose-mediated hypertrophic responses in the kidney.

  19. Using High-Precision Signaling Activity Imaging to Personalize Ras Pathway Inhibition Strategies in Neurofibromatosis

    Science.gov (United States)

    2017-06-01

    cell types and genetic contexts relevant to NF1. During this award period, we have improved methodologies for introducing genetically encoded...shown that the kinetics of ERK and Akt activation, including the intensity, duration, and probability of response, are critical for deciding how the...and genetic configurations relevant to NF1. We will assess whether NF1 mutants cells differ in signaling intensity, duration, threshold, or basal

  20. Nitric oxide modulation of the basal ganglia circuitry: therapeutic implication for Parkinson's disease and other motor disorders.

    Science.gov (United States)

    Pierucci, Massimo; Galati, Salvatore; Valentino, Mario; Di Matteo, Vincenzo; Benigno, Arcangelo; Pitruzzella, Alessandro; Muscat, Richard; Di Giovanni, Giuseppe

    2011-11-01

    Several recent studies have emphasized a crucial role for the nitrergic system in movement control and the pathophysiology of the basal ganglia (BG). These observations are supported by anatomical evidence demonstrating the presence of nitric oxide synthase (NOS) in all the basal ganglia nuclei. In fact, nitrergic terminals have been reported to make synaptic contacts with both substantia nigra dopamine-containing neurons and their terminal areas such as the striatum, the globus pallidus and the subthalamus. These brain areas contain a high expression of nitric oxide (NO)-producing neurons, with the striatum having the greatest number, together with important NO afferent input. In this paper, the distribution of NO in the BG nuclei will be described. Furthermore, evidence demonstrating the nitrergic control of BG activity will be reviewed. The new avenues that the increasing knowledge of NO in motor control has opened for exploring the pathophysiology and pharmacology of Parkinson's disease and other movement disorders will be discussed. For example, inhibition of striatal NO/guanosine monophosphate signal pathway by phosphodiesterases seems to be effective in levodopa-induced dyskinesia. However, the results of experimental studies have to be interpreted with caution given the complexities of nitrergic signalling and the limitations of animal models. Nevertheless, the NO system represents a promising pharmacological intervention for treating Parkinson's disease and related disorders.

  1. A frontal cortex event-related potential driven by the basal forebrain

    Science.gov (United States)

    Nguyen, David P; Lin, Shih-Chieh

    2014-01-01

    Event-related potentials (ERPs) are widely used in both healthy and neuropsychiatric conditions as physiological indices of cognitive functions. Contrary to the common belief that cognitive ERPs are generated by local activity within the cerebral cortex, here we show that an attention-related ERP in the frontal cortex is correlated with, and likely generated by, subcortical inputs from the basal forebrain (BF). In rats performing an auditory oddball task, both the amplitude and timing of the frontal ERP were coupled with BF neuronal activity in single trials. The local field potentials (LFPs) associated with the frontal ERP, concentrated in deep cortical layers corresponding to the zone of BF input, were similarly coupled with BF activity and consistently triggered by BF electrical stimulation within 5–10 msec. These results highlight the important and previously unrecognized role of long-range subcortical inputs from the BF in the generation of cognitive ERPs. DOI: http://dx.doi.org/10.7554/eLife.02148.001 PMID:24714497

  2. Availability of streamflow for recharge of the basal aquifer in the Pearl Harbor area, Hawaii

    Science.gov (United States)

    Hirashima, George Tokusuke

    1971-01-01

    The Pearl Harbor area is underlain by an extensive basal aquifer that contains large supplies of fresh water. Because of the presence of a cap rock composed of sedimentary material that is less permeable than the basaltic lava of the basal aquifer, seaward movement of ground water is retarded. The cap rock causes the basal water to stand at a high level; thus, the lens of fresh water that floats on sea water is thick. Discharge from the basal ground-water body, which includes pumpage from wells and shafts, averaged 250 million gallons per day during 1931-65. Because the water level in the basal aquifer did not decline progressively, recharge to the ground-water body must have been approximately equal to discharge. Although pumping for agricultural use has decreased since 1931, net ground-water discharge has increased because of a large increase in pumping for urban use. Substitution of ground water for surface water in the irrigation of sugarcane has also contributed to a net increase in ground-water discharge. The development of Mililani Town will further increase discharge. The increase in ground-water discharge may cause an increase in chloride content of the water pumped from wells near the shore of Pearl Harbor unless the increased discharge is balanced by increased recharge to the local aquifer. The aquifer is recharged by direct infiltration and deep percolation of rain, principally in the high forested area, by infiltration and percolation of irrigation water applied in excess of plant requirements, by seepage of water through streambeds, and possibly by ground-water inflow from outside the area. Recharge is greatest in the uplands, where rainfall is heavy and where much infiltration takes place before rainwater collects in the middle and lower reaches of stream channels. Once water collects in and saturates the alluvium of stream channels, additional inflow to the streams will flow out to sea, only slightly decreased by seepage. Average annual direct

  3. Basal and adenosine receptor-stimulated levels of cAMP are reduced in lymphocytes from alcoholic patients

    International Nuclear Information System (INIS)

    Diamond, I.; Wrubel, B.; Estrin, W.; Gordon, A.

    1987-01-01

    Alcoholism causes serious neurologic disease that may be due, in part, to the ability of ethanol to interact with neural cell membranes and change neuronal function. Adenosine receptors are membrane-bound proteins that appear to mediate some of the effects of ethanol in the brain. Human lymphocytes also have adenosine receptors, and their activation causes increases in cAMP levels. To test the hypothesis that basal and adenosine receptor-stimulated cAMP levels in lymphocytes might be abnormal in alcoholism, the authors studied lymphocytes from 10 alcoholic subjects, 10 age- and sex-matched normal individuals, and 10 patients with nonalcoholic liver disease. Basal and adenosine receptor-stimulated cAMP levels were reduced 75% in lymphocytes from alcoholic subjects. Also, there was a 76% reduction in ethanol stimulation of cAMP accumulation in lymphocytes from alcoholics. Similar results were demonstrable in isolated T cells. Unlike other laboratory tests examined, these measurements appeared to distinguish alcoholics from normal subjects and from patients with nonalcoholic liver disease. Reduced basal and adenosine receptor-stimulated levels of cAMP in lymphocytes from alcoholics may reflect a change in cell membranes due either to chronic alcohol abuse or to a genetic predisposition unique to alcoholic subjects

  4. Optical coherence tomography of basal cell carcinoma

    DEFF Research Database (Denmark)

    Yücel, D.; Themstrup, L.; Manfredi, Maddalena

    2016-01-01

    Background: Basal cell carcinoma (BCC) is the most prevalent malignancy in Caucasians. Optical coherence tomography (OCT) is a non-invasive optical imaging technology using the principle of interferometry. OCT has shown a great potential in diagnosing, monitoring, and follow-up of BCC. So far most...

  5. Basal cell carcinoma on the left cheek

    International Nuclear Information System (INIS)

    Jancar, B.

    2007-01-01

    A 91-year-old female patient was treated with irradiation for histologically confirmed basal cell carcinoma on the left cheek. The tumour, measuring 3 x 3 cm, with the depth of 2 cm, was extending up to the lower lid of the left eye. (author)

  6. Deep RNA-Seq analysis reveals unexpected features of human prostate basal epithelial cells

    Directory of Open Access Journals (Sweden)

    Dingxiao Zhang

    2016-03-01

    Full Text Available Prostate cancer is the second leading cause of cancer-related deaths among American men [1]. The prostate gland mainly contains basal and luminal cells, which are constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. Here, for the first time, we describe a whole-genome transcriptome analysis of human benign prostatic basal and luminal populations by using deep RNA sequencing (GSE67070 [2]. Combined with comprehensive molecular and biological characterizations, we show that the differential gene expression profiles account for their distinct functional phenotypes. Strikingly, in contrast to luminal cells, basal cells preferentially express gene categories associated with stem cells, neural and neuronal development, and RNA processing. Of clinical relevance, the treatment failed castration-resistant and anaplastic prostate cancers molecularly resemble a basal-like phenotype. We also identified genes associated with patient clinical outcome. Therefore, we provide a gene expression resource for understanding human prostate epithelial lineages, and link the cell-type specific gene signatures to subtypes of prostate cancer development. Keywords: Prostate epithelial cells, Basal cells, Luminal cells, RNA-seq

  7. Cyclical and patch-like GDNF distribution along the basal surface of Sertoli cells in mouse and hamster testes.

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    Takeshi Sato

    Full Text Available BACKGROUND AND AIMS: In mammalian spermatogenesis, glial cell line-derived neurotrophic factor (GDNF is one of the major Sertoli cell-derived factors which regulates the maintenance of undifferentiated spermatogonia including spermatogonial stem cells (SSCs through GDNF family receptor α1 (GFRα1. It remains unclear as to when, where and how GDNF molecules are produced and exposed to the GFRα1-positive spermatogonia in vivo. METHODOLOGY AND PRINCIPAL FINDINGS: Here we show the cyclical and patch-like distribution of immunoreactive GDNF-positive signals and their close co-localization with a subpopulation of GFRα1-positive spermatogonia along the basal surface of Sertoli cells in mice and hamsters. Anti-GDNF section immunostaining revealed that GDNF-positive signals are mainly cytoplasmic and observed specifically in the Sertoli cells in a species-specific as well as a seminiferous cycle- and spermatogenic activity-dependent manner. In contrast to the ubiquitous GDNF signals in mouse testes, high levels of its signals were cyclically observed in hamster testes prior to spermiation. Whole-mount anti-GDNF staining of the seminiferous tubules successfully visualized the cyclical and patch-like extracellular distribution of GDNF-positive granular deposits along the basal surface of Sertoli cells in both species. Double-staining of GDNF and GFRα1 demonstrated the close co-localization of GDNF deposits and a subpopulation of GFRα1-positive spermatogonia. In both species, GFRα1-positive cells showed a slender bipolar shape as well as a tendency for increased cell numbers in the GDNF-enriched area, as compared with those in the GDNF-low/negative area of the seminiferous tubules. CONCLUSION/SIGNIFICANCE: Our data provide direct evidence of regionally defined patch-like GDNF-positive signal site in which GFRα1-positive spermatogonia possibly interact with GDNF in the basal compartment of the seminiferous tubules.

  8. Recurrent odontogenic keratocysts in basal cell nevus syndrome: report of a case

    International Nuclear Information System (INIS)

    Lee, Byung Do; Kim, Jin Hoa; Choi, Dong Hoon; Koh, Kwang Soo; Lee, Sang Rae

    2004-01-01

    Basal cell nevus syndrome (BCNS) is principally characterized by cutaneous basal cell carcinomas, multiple odontogenic keratocysts and skeletal abnormalities. Our patient represented several characteristics of BCNS, such as, multiple odontogenic keratocysts, facial nevus, calcification of falx cerebri, parietal bossing and mental retardation. The cyst on posterior mandible showed recurrent and newly developing tendency.

  9. Lixisenatide as add-on therapy to basal insulin

    Directory of Open Access Journals (Sweden)

    Brown DX

    2013-12-01

    Full Text Available Dominique Xavier Brown, Emma Louise Butler, Marc Evans Diabetes Department, University Hospital Llandough, Cardiff, UK Abstract: Many patients with type 2 diabetes mellitus do not achieve target glycosylated hemoglobin A1c levels despite optimally titrated basal insulin and satisfactory fasting plasma glucose levels. Current evidence suggests that HbA1c levels are dictated by both basal glucose and postprandial glucose levels. This has led to a consensus that postprandial glucose excursions contribute to poor glycemic control in these patients. Lixisenatide is a once-daily, prandial glucagon-like peptide 1 (GLP-1 receptor agonist with a four-fold affinity for the GLP-1 receptor compared with native GLP-1. Importantly, lixisenatide causes a significant delay in gastric emptying time, an important determinant of the once-daily dosing regimen. An exendin-4 mimetic with six lysine residues removed at the C-terminal, lixisenatide has pronounced postprandial glucose-lowering effects, making it a novel incretin agent for use in combination with optimally titrated basal insulin. Lixisenatide exerts profound effects on postprandial glucose through established mechanisms of glucose-dependent insulin secretion and glucagon suppression in combination with delayed gastric emptying. This review discusses the likely place that lixisenatide will occupy in clinical practice, given its profound effects on postprandial glucose and potential to reduce glycemic variability. Keywords: lixisenatide, add-on therapy, insulin, GLP-1 receptor agonist, postprandial glucose, pharmacodynamics

  10. Functional Neuroanatomy and Behavioural Correlates of the Basal Ganglia: Evidence from Lesion Studies

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    Peter Ward

    2013-01-01

    Full Text Available Introduction: The basal ganglia are interconnected with cortical areas involved in behavioural, cognitive and emotional processes, in addition to movement regulation. Little is known about which of these functions are associated with individual basal ganglia substructures.

  11. Pigmented basal cell carcinoma of the eyelid in Hispanics

    Directory of Open Access Journals (Sweden)

    Lily Koo Lin

    2008-10-01

    Full Text Available Lily Koo Lin1, Han Lee2, Eli Chang11Department of Oculoplastics, Doheny Eye Institute, Los Angeles, CA, USA; 2Department of Dermatology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USABackground: Pigmented basal cell carcinoma (PBCC of the eyelid has not been well cited in the literature, and is often overlooked in the differential diagnosis of pigmented eyelid lesions. We aim to describe PBCC of the eyelid in Hispanic patients.Methods: Retrospective review of patients with eyelid skin cancer who presented to the Department of Dermatology at the Keck School of Medicine of the University of Southern California and the Doheny Eye Institute from January 2002 to November 2005.Results: Sixty-nine of the 79 patients with eyelid skin cancer had basal cell carcinoma. Eight of these patients were Hispanic. Four of the eight Hispanic patients had PBCC.Conclusions: Although eyelid PBCC is regarded as a rare condition, it may occur more commonly in the Hispanic population and should be remembered in the differential diagnosis of pigmented eyelid lesions.Keywords: pigmented basal cell carcinoma, eyelid, skin cancer, lesions

  12. Bacterial diversity of oil palm Elaeis guineensis basal stems

    Science.gov (United States)

    Amran, Afzufira; Jangi, Mohd Sanusi; Aqma, Wan Syaidatul; Yusof, Nurul Yuziana Mohd; Bakar, Mohd Faizal Abu; Isa, Mohd Noor Mat

    2016-11-01

    Oil palm, Elaeis guineensis is one of the major industrial production crops in Malaysia. Basal stem rot, caused by the white fungus, Ganoderma boninense, is a disease that reduces oil palm yields in most production areas of the world. Understanding of bacterial community that is associated with Ganoderma infection will shed light on how this bacterial community contributes toward the severity of the infection. In this preliminary study, we assessed the bacterial community that inhabit the basal stems of E. guineensis based on 16S rRNA gene as a marker using next generation sequencing platform. This result showed that a total of 84,372 operational taxonomic-units (OTUs) were identified within six samples analyzed. A total 55,049 OTUs were assigned to known taxonomy whereas 29,323 were unassigned. Cyanobacteria, Bacteroidetes, Firmicutes and Proteobacteria were the most abundant phyla found in all six samples and the unique taxonomy assigned for each infected and healthy samples were also identified. The findings from this study will further enhance our knowledge in the interaction of bacterial communities against Ganoderma infection within the oil palm host plant and for a better management of the basal stems rot disease.

  13. Validação de equações de predição da taxa metabólica basal em mulheres residentes em Porto Alegre, RS, Brasil Validation of predictive equations of basal metabolic rate of women living in Southern Brazil

    Directory of Open Access Journals (Sweden)

    Vivian Wahrlich

    2001-02-01

    Full Text Available OBJETIVO: Medir a taxa metabólica basal em mulheres de 20 a 40 anos, não-gestantes ou lactantes, e comparar o valor medido com os valores de taxa metabólica basal estimados por equações de predição. MÉTODOS: A taxa metabólica basal foi medida por calorimetria indireta, pela manhã, durante a fase folicular do ciclo menstrual, em 60 voluntárias residentes no município de Porto Alegre, RS, sob condições padronizadas de jejum, repouso e ambiente. RESULTADOS: A média (± desvio-padrão da taxa metabólica basal medida foi 1.185,3±148,6 kcal em 24 horas. A taxa metabólica basal, estimada por equações, foi significativamente maior (7% a 17% do que a taxa metabólica basal medida. CONCLUSÕES: Os dados evidenciaram que as equações de predição não são adequadas para estimar a taxa metabólica basal nas mulheres avaliadas. O emprego dessas equações podem superestimar os requerimentos energéticos para mulheres com características semelhantes.OBJECTIVE: To measure the basal metabolic rate of women (aged 20 to 40 years living in Porto Alegre, Brazil, and to compare it with estimated values bored on published predictive equations. METHODS: Basal metabolic rate was measured by indirect calorimetry under standard conditions in the follicular phase of the menstrual cycle of 60 volunteers. RESULTS: Mean measured basal metabolic rate (± standard deviation was 1,185.3± 148.6 kcal/24 hours. Estimated basal metabolic rates were significantly greater (7% to 17% than measured basal metabolic rate (p<0.0001. CONCLUSIONS: These results show that predictive equations are not suitable to estimate basal metabolic rate in these groups of women and that the use of estimated basal metabolic rate will lead to an overestimation of energy requirements in women with similar characteristics.

  14. Prediction of BRCA1 status in patients with breast cancer using estrogen receptor and basal phenotype

    NARCIS (Netherlands)

    Lakhani, Sunil R.; Reis-Filho, Jorge S.; Fulford, Laura; Penault-Llorca, Frederique; van der Vijver, Marc; Parry, Suzanne; Bishop, Timothy; Benitez, Javier; Rivas, Carmen; Bignon, Yves-Jean; Chang-Claude, Jenny; Hamann, Ute; Cornelisse, Cees J.; Devilee, Peter; Beckmann, Matthias W.; Nestle-Krämling, Carolin; Daly, Peter A.; Haites, Neva; Varley, Jenny; Lalloo, Fiona; Evans, Gareth; Maugard, Christine; Meijers-Heijboer, Hanne; Klijn, Jan G. M.; Olah, Edith; Gusterson, Barry A.; Pilotti, Silvana; Radice, Paolo; Scherneck, Siegfried; Sobol, Hagay; Jacquemier, Jocelyne; Wagner, Teresa; Peto, Julian; Stratton, Michael R.; McGuffog, Lesley; Easton, Douglas F.

    2005-01-01

    To investigate the proportion of breast cancers arising in patients with germ line BRCA1 and BRCA2 mutations expressing basal markers and developing predictive tests for identification of high-risk patients. Histopathologic material from 182 tumors in BRCA1 mutation carriers, 63 BRCA2 carriers, and

  15. Development and Application of a Microfluidics-Based Panel in the Basal/Luminal Transcriptional Characterization of Archival Bladder Cancers.

    Directory of Open Access Journals (Sweden)

    Doris Kim

    Full Text Available In the age of personalized medicine stratifying tumors into molecularly defined subtypes associated with distinctive clinical behaviors and predictable responses to therapies holds tremendous value. Towards this end, we developed a custom microfluidics-based bladder cancer gene expression panel for characterization of archival clinical samples. In silico analysis indicated that the content of our panel was capable of accurately segregating bladder cancers from several public datasets into the clinically relevant basal and luminal subtypes. On a technical level, our bladder cancer panel yielded robust and reproducible results when analyzing formalin-fixed, paraffin-embedded (FFPE tissues. We applied our panel in the analysis of a novel set of 204 FFPE samples that included non-muscle invasive bladder cancers (NMIBCs, muscle invasive disease (MIBCs, and bladder cancer metastases (METs. We found NMIBCs to be mostly luminal-like, MIBCs to include both luminal- and basal-like types, and METs to be predominantly of a basal-like transcriptional profile. Mutational analysis confirmed the expected enrichment of FGFR3 mutations in luminal samples, and, consistently, FGFR3 IHC showed high protein expression levels of the receptor in these tumors. Our bladder cancer panel enables basal/luminal characterization of FFPE tissues and with further development could be used for stratification of bladder cancer samples in the clinic.

  16. Sleep-wake sensitive mechanisms of adenosine release in the basal forebrain of rodents: an in vitro study.

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    Robert Edward Sims

    Full Text Available Adenosine acting in the basal forebrain is a key mediator of sleep homeostasis. Extracellular adenosine concentrations increase during wakefulness, especially during prolonged wakefulness and lead to increased sleep pressure and subsequent rebound sleep. The release of endogenous adenosine during the sleep-wake cycle has mainly been studied in vivo with microdialysis techniques. The biochemical changes that accompany sleep-wake status may be preserved in vitro. We have therefore used adenosine-sensitive biosensors in slices of the basal forebrain (BFB to study both depolarization-evoked adenosine release and the steady state adenosine tone in rats, mice and hamsters. Adenosine release was evoked by high K(+, AMPA, NMDA and mGlu receptor agonists, but not by other transmitters associated with wakefulness such as orexin, histamine or neurotensin. Evoked and basal adenosine release in the BFB in vitro exhibited three key features: the magnitude of each varied systematically with the diurnal time at which the animal was sacrificed; sleep deprivation prior to sacrifice greatly increased both evoked adenosine release and the basal tone; and the enhancement of evoked adenosine release and basal tone resulting from sleep deprivation was reversed by the inducible nitric oxide synthase (iNOS inhibitor, 1400 W. These data indicate that characteristics of adenosine release recorded in the BFB in vitro reflect those that have been linked in vivo to the homeostatic control of sleep. Our results provide methodologically independent support for a key role for induction of iNOS as a trigger for enhanced adenosine release following sleep deprivation and suggest that this induction may constitute a biochemical memory of this state.

  17. Comparison of liraglutide plus basal insulin and basal-bolus insulin therapy (BBIT) for glycemic control, body weight stability, and treatment satisfaction in patients treated using BBIT for type 2 diabetes without severe insulin deficiency: A randomized prospective pilot study.

    Science.gov (United States)

    Yamamoto, Saki; Hayashi, Toshiyuki; Ohara, Makoto; Goto, Satoshi; Sato, Jun; Nagaike, Hiroe; Fukase, Ayako; Sato, Nobuko; Hiromura, Munenori; Tomoyasu, Masako; Nakanishi, Noriko; Lee, Soushou; Osamura, Anna; Yamamoto, Takeshi; Fukui, Tomoyasu; Hirano, Tsutomu

    2018-03-26

    We examined whether 0.9 mg/day liraglutide plus basal insulin (Lira-basal) is superior to basal-bolus insulin therapy (BBIT) for type 2 diabetes (T2DM) without severe insulin deficiency as determined by glucagon stimulation. Fifty patients receiving BBIT were enrolled in this 24-week, prospective, randomized, open-labeled study. After excluding subjects with fasting C-peptide immunoreactivity (CPR) basal (n = 12) or continued BBIT (n = 13). Primary endpoint was change in HbA1c. Secondary endpoints were changes in body weight (BW), 7-point self-monitored blood glucose (SMBG), and Diabetes Treatment Satisfaction Questionnaire status (DTSQs) scores. The Lira-basal group demonstrated reduced HbA1c, whereas the BBIT group showed no change. BW was reduced in the Lira-basal group but increased in the BBIT group. The Lira-basal group also exhibited significantly reduced pre-breakfast and pre-lunch SMBG. DTSQs scores improved in the Lira-basal group but not the BBIT group. Plasma lipids, liver function, and kidney function were not significantly changed in either group. Lira-basal therapy is superior to BBIT for T2DM without severe insulin deficiency. This study was registered with UMIN Clinical Trials Registry (UMIN000028313). Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  18. Preferential antitumor effect of the Src inhibitor dasatinib associated with a decreased proportion of aldehyde dehydrogenase 1-positive cells in breast cancer cells of the basal B subtype

    Directory of Open Access Journals (Sweden)

    Watanabe Mika

    2010-10-01

    Full Text Available Abstract Background Recent studies have suggested that the Src inhibitor dasatinib preferentially inhibits the growth of breast cancer cells of the basal-like subtype. To clarify this finding and further investigate combined antitumor effects of dasatinib with cytotoxic agents, a panel of breast cancer cell lines of various subtypes was treated with dasatinib and/or chemotherapeutic agents. Methods Seven human breast cancer cell lines were treated with dasatinib and/or seven chemotherapeutic agents. Effects of the treatments on c-Src activation, cell growth, cell cycle, apoptosis and the proportion of aldehyde dehydrogenase (ALDH 1-positive cells were examined. Results The 50%-growth inhibitory concentrations (IC50s of dasatinib were much lower in two basal B cell lines than those in the other cell lines. The IC50s of chemotherapeutic agents were not substantially different among the cell lines. Dasatinib enhanced antitumor activity of etoposide in the basal B cell lines. Dasatinib induced a G1-S blockade with a slight apoptosis, and a combined treatment of dasatinib with etoposide also induced a G1-S blockade in the basal B cell lines. Dasatinib decreased the expression levels of phosphorylated Src in all cell lines. Interestingly, dasatinib significantly decreased the proportion of ALDH1-positive cells in the basal B cell lines but not in the other cell lines. Conclusions The present study indicates that dasatinib preferentially inhibits the growth of breast cancer cells of the basal B subtype associated with a significant loss of putative cancer stem cell population. A combined use of dasatinib with etoposide additively inhibits their growth. Further studies targeting breast cancers of the basal B subtype using dasatinib with cytotoxic agents are warranted.

  19. Involvement of dopamine loss in extrastriatal basal ganglia nuclei in the pathophysiology of Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    Abdelhamid eBenazzouz

    2014-05-01

    Full Text Available Parkinson’s disease is a neurological disorder characterized by the manifestation of motor symptoms, such as akinesia, muscle rigidity and tremor at rest. These symptoms are classically attributed to the degeneration of dopamine neurons in the pars compacta of substantia nigra (SNc, which results in a marked dopamine depletion in the striatum. It is well established that dopamine neurons in the SNc innervate not only the striatum, which is the main target, but also other basal ganglia nuclei including the two segments of globus pallidus and the subthalamic nucleus. The role of dopamine and its depletion in the striatum is well known, however, the role of dopamine depletion in the pallidal complex and the subthalamic nucleus in the genesis of their abnormal neuronal activity and in parkinsonian motor deficits is still not clearly determined. Based on recent experimental data from animal models of Parkinson's disease in rodents and non-human primates and also from parkinsonian patients, this review summarizes current knowledge on the role of dopamine in the modulation of basal ganglia neuronal activity and also the role of dopamine depletion in these nuclei in the pathophysiology of Parkinson's disease.

  20. Nevoid Basal-Cell Syndrome: literature review and case report in a family

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    Alfio José Tincani

    Full Text Available The Nevoid Basal-Cell Carcinoma Syndrome (NBCC, or as it is also referred to, basal-cell nevus syndrome or Gorlin-Goltz syndrome, is characterized by multiple early-appearing basal cell carcinomas, keratocytosis of the mandible, and anomalies of the ocular, skeletal reproductive system. We describe four patients in the same family, all of them possessing a large number of skin tumors associated with other typical clinical and X-Ray anomalies of NBCC. The definitive treatment of NBCC has yet to be established, however, early diagnosis is very important as well as the periodical follow-up examination of ten patients, mainly due to the transformations in the skin lesions that may occur.

  1. Visual training paired with electrical stimulation of the basal forebrain improves orientation-selective visual acuity in the rat.

    Science.gov (United States)

    Kang, Jun Il; Groleau, Marianne; Dotigny, Florence; Giguère, Hugo; Vaucher, Elvire

    2014-07-01

    The cholinergic afferents from the basal forebrain to the primary visual cortex play a key role in visual attention and cortical plasticity. These afferent fibers modulate acute and long-term responses of visual neurons to specific stimuli. The present study evaluates whether this cholinergic modulation of visual neurons results in cortical activity and visual perception changes. Awake adult rats were exposed repeatedly for 2 weeks to an orientation-specific grating with or without coupling this visual stimulation to an electrical stimulation of the basal forebrain. The visual acuity, as measured using a visual water maze before and after the exposure to the orientation-specific grating, was increased in the group of trained rats with simultaneous basal forebrain/visual stimulation. The increase in visual acuity was not observed when visual training or basal forebrain stimulation was performed separately or when cholinergic fibers were selectively lesioned prior to the visual stimulation. The visual evoked potentials show a long-lasting increase in cortical reactivity of the primary visual cortex after coupled visual/cholinergic stimulation, as well as c-Fos immunoreactivity of both pyramidal and GABAergic interneuron. These findings demonstrate that when coupled with visual training, the cholinergic system improves visual performance for the trained orientation probably through enhancement of attentional processes and cortical plasticity in V1 related to the ratio of excitatory/inhibitory inputs. This study opens the possibility of establishing efficient rehabilitation strategies for facilitating visual capacity.

  2. New basal iguanodonts from the Cedar Mountain formation of Utah and the evolution of thumb-spiked dinosaurs.

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    Andrew T McDonald

    Full Text Available BACKGROUND: Basal iguanodontian dinosaurs were extremely successful animals, found in great abundance and diversity almost worldwide during the Early Cretaceous. In contrast to Europe and Asia, the North American record of Early Cretaceous basal iguanodonts has until recently been limited largely to skulls and skeletons of Tenontosaurus tilletti. METHODOLOGY/PRINCIPAL FINDINGS: Herein we describe two new basal iguanodonts from the Yellow Cat Member of the Cedar Mountain Formation of eastern Utah, each known from a partial skull and skeleton. Iguanacolossus fortis gen. et sp. nov. and Hippodraco scutodens gen. et sp. nov. are each diagnosed by a single autapomorphy and a unique combination of characters. CONCLUSIONS/SIGNIFICANCE: Iguanacolossus and Hippodraco add greatly to our knowledge of North American basal iguanodonts and prompt a new comprehensive phylogenetic analysis of basal iguanodont relationships. This analysis indicates that North American Early Cretaceous basal iguanodonts are more basal than their contemporaries in Europe and Asia.

  3. New Basal Iguanodonts from the Cedar Mountain Formation of Utah and the Evolution of Thumb-Spiked Dinosaurs

    Science.gov (United States)

    McDonald, Andrew T.; Kirkland, James I.; DeBlieux, Donald D.; Madsen, Scott K.; Cavin, Jennifer; Milner, Andrew R. C.; Panzarin, Lukas

    2010-01-01

    Background Basal iguanodontian dinosaurs were extremely successful animals, found in great abundance and diversity almost worldwide during the Early Cretaceous. In contrast to Europe and Asia, the North American record of Early Cretaceous basal iguanodonts has until recently been limited largely to skulls and skeletons of Tenontosaurus tilletti. Methodology/Principal Findings Herein we describe two new basal iguanodonts from the Yellow Cat Member of the Cedar Mountain Formation of eastern Utah, each known from a partial skull and skeleton. Iguanacolossus fortis gen. et sp. nov. and Hippodraco scutodens gen. et sp. nov. are each diagnosed by a single autapomorphy and a unique combination of characters. Conclusions/Significance Iguanacolossus and Hippodraco add greatly to our knowledge of North American basal iguanodonts and prompt a new comprehensive phylogenetic analysis of basal iguanodont relationships. This analysis indicates that North American Early Cretaceous basal iguanodonts are more basal than their contemporaries in Europe and Asia. PMID:21124919

  4. Modern basal insulins: an ongoing story or the start of a new era?

    Directory of Open Access Journals (Sweden)

    Ivan Ivanovich Dedov

    2015-11-01

    Full Text Available Basal insulin represents an essential tool in the treatment of both type 1 and type 2 diabetes mellitus. The development of insulin analogues has improved the possibilities of diabetes treatment. Despite significant progress in understanding the physiology, chemistry, kinetics and action of insulin, currently available basal insulin products do not optimally mimic the endogenous profile of insulin. Although basal insulin analogues have some advantages over neutral protamine Hagedorn insulin in diabetes treatment, hypoglycaemia remains the main problem in the achievement of optimal glycaemic control in most patients with diabetes. These unmet clinical needs have stimulated the development of new basal insulin analogues with improved pharmacological profiles. This article reviews the specific characteristics of new long-acting insulin analogues to try and understand their benefits and limitations in the improvement of diabetes management and their possibilities in physiologic and safe insulin replacement.

  5. Basal hyperaemia is the primary abnormality of perfusion in Takotsubo cardiomyopathy

    DEFF Research Database (Denmark)

    Christensen, Thomas Emil; Ahtarovski, Kiril Aleksov; Bang, Lia Evi

    2015-01-01

    AIMS: Takotsubo cardiomyopathy (TTC) is characterized by acute completely reversible regional left ventricle (LV) akinesia and decreased tracer uptake in the akinetic region on semi-quantitative perfusion imaging. The latter may be due to normoperfusion of the akinetic mid/apical area and basal...... hyperperfusion. Our aim was to examine abnormalities of perfusion in TTC, and we hypothesized that basal hyperperfusion is the primary perfusion abnormality in the acute state. METHOD AND RESULTS: Twenty-five patients were diagnosed with TTC due to (i) acute onset of symptoms, (ii) typical apical ballooning......-on follow-up. Patients initially had severe heart failure, mid/apical oedema but no infarction, and a rise in cardiac biomarkers. On initial perfusion PET imaging, eight patients appeared to have normal, whereas 17 patients had impaired LV perfusion. In the latter, flow in the basal region was increased...

  6. In-situ analysis of the slip activity during tensile deformation of cast and extruded Mg-10Gd-3Y-0.5Zr (wt.%) at 250 °C

    Energy Technology Data Exchange (ETDEWEB)

    Wang, H. [National Engineering Research Center of Light Alloy Net Forming, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240 (China); The State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240 (China); Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, MI 48824 (United States); Boehlert, C.J., E-mail: boehlert@egr.msu.edu [Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, MI 48824 (United States); Wang, Q.D., E-mail: wangqudong@sjtu.edu.cn [National Engineering Research Center of Light Alloy Net Forming, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240 (China); The State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240 (China); Yin, D.D. [Key Laboratory of Advanced Materials Technology under Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu, Sichuan 610031 (China); Ding, W.J. [National Engineering Research Center of Light Alloy Net Forming, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240 (China); The State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240 (China)

    2016-06-15

    The slip activity and slip interaction in tensile deformation of peak-aged cast and extruded Mg-10Gd-3Y-0.5Zr (wt.%) at 250 °C was investigated using in-situ scanning electron microscopy. Basal slip was the most likely system to be activated during the tensile deformation, while prismatic < a > and pyramidal < c + a > slip also contributed to the deformation. No twinning was observed. The number of non-basal slip systems accounted for ~ 36% of the total active slip systems for the cast alloy, while non-basal slip accounted for 12–17% of the total deformation observations in the extruded alloy. Multiple-slip was observed within grains, and the basal/prismatic pairing type dominated the multiple-slip observations. Slip transfer occurred across grain boundaries and most of the slip transfer observations showed basal-basal type. The involved slip systems of slip transfer pairs were always associated with the same < a > direction. The slip transfer occurred more easily at low angle boundaries (LABs) and boundaries with misorientations greater than 75°. - Highlights: • Slip deformation of a Mg-RE alloy at 250 °C was investigated using in-situ SEM. • The extruded-T5 GW103 alloy did not exhibit a high anisotropic behavior. • Multiple-slip was observed within grains, and basal/prismatic type dominated. • Slip transfer occurred and most of the observations showed basal-basal type. • Slip transfer occurred more easily at LABs and boundaries with misorientations > 75°.

  7. Silibinin and Its 2,3-Dehydro-Derivative Inhibit Basal Cell Carcinoma Growth via Suppression of Mitogenic Signaling and Transcription Factors Activation

    Czech Academy of Sciences Publication Activity Database

    Tilley, C.; Deep, G.; Agarwal, Ch.; Wempe, M.F.; Biedermann, David; Valentová, Kateřina; Křen, Vladimír; Agarwal, R.

    2016-01-01

    Roč. 55, č. 1 (2016), s. 3-14 ISSN 0899-1987 R&D Projects: GA MŠk LH13097 Institutional support: RVO:61388971 Keywords : basal cell carcinoma * chemoprevention * phytochemicals Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 4.185, year: 2016

  8. Identification of Personalized Chemoresistance Genes in Subtypes of Basal-Like Breast Cancer Based on Functional Differences Using Pathway Analysis.

    Directory of Open Access Journals (Sweden)

    Tong Wu

    Full Text Available Breast cancer is a highly heterogeneous disease that is clinically classified into several subtypes. Among these subtypes, basal-like breast cancer largely overlaps with triple-negative breast cancer (TNBC, and these two groups are generally studied together as a single entity. Differences in the molecular makeup of breast cancers can result in different treatment strategies and prognoses for patients with different breast cancer subtypes. Compared with other subtypes, basal-like and other ER+ breast cancer subtypes exhibit marked differences in etiologic factors, clinical characteristics and therapeutic potential. Anthracycline drugs are typically used as the first-line clinical treatment for basal-like breast cancer subtypes. However, certain patients develop drug resistance following chemotherapy, which can lead to disease relapse and death. Even among patients with basal-like breast cancer, there can be significant molecular differences, and it is difficult to identify specific drug resistance proteins in any given patient using conventional variance testing methods. Therefore, we designed a new method for identifying drug resistance genes. Subgroups, personalized biomarkers, and therapy targets were identified using cluster analysis of differentially expressed genes. We found that basal-like breast cancer could be further divided into at least four distinct subgroups, including two groups at risk for drug resistance and two groups characterized by sensitivity to pharmacotherapy. Based on functional differences among these subgroups, we identified nine biomarkers related to drug resistance: SYK, LCK, GAB2, PAWR, PPARG, MDFI, ZAP70, CIITA and ACTA1. Finally, based on the deviation scores of the examined pathways, 16 pathways were shown to exhibit varying degrees of abnormality in the various subgroups, indicating that patients with different subtypes of basal-like breast cancer can be characterized by differences in the functional status of

  9. Cancer associated fibroblasts (CAFs) are activated in cutaneous basal cell carcinoma and in the peritumoural skin.

    Science.gov (United States)

    Omland, Silje Haukali; Wettergren, Erika Elgstrand; Mollerup, Sarah; Asplund, Maria; Mourier, Tobias; Hansen, Anders Johannes; Gniadecki, Robert

    2017-10-07

    Cutaneous basal cell carcinoma (BCC) is the commonest cancer worldwide. BCC is locally invasive and the surrounding stromal microenvironment is pivotal for tumourigenesis. Cancer associated fibroblasts (CAFs) in the microenvironment are essential for tumour growth in a variety of neoplasms but their role in BCC is poorly understood. Material included facial BCC and control skin from the peritumoural area and from the buttocks. With next-generation sequencing (NGS) we compared mRNA expression between BCC and peritumoural skin. qRT-PCR, immunohistochemical and immunofluorescent staining were performed to validate the NGS results and to investigate CAF-related cyto-and chemokines. NGS revealed upregulation of 65 genes in BCC coding for extracellular matrix components pointing at CAF-related matrix remodeling. qRT-PCR showed increased mRNA expression of CAF markers FAP-α, PDGFR-β and prolyl-4-hydroxylase in BCC. Peritumoural skin (but not buttock skin) also exhibited high expression of PDGFR-β and prolyl-4-hydroxylase but not FAP-α. We found a similar pattern for the CAF-associated chemokines CCL17, CCL18, CCL22, CCL25, CXCL12 and IL6 with high expression in BCC and peritumoural skin but absence in buttock skin. Immunofluorescence revealed correlation between FAP-α and PDGFR-β and CXCL12 and CCL17. Matrix remodeling is the most prominent molecular feature of BCC. CAFs are present within BCC stroma and associated with increased expression of chemokines involved in tumour progression and immunosuppression (CXCL12, CCL17). Fibroblasts from chronically sun-exposed skin near tumours show gene expression patterns resembling that of CAFs, indicating that stromal fibroblasts in cancer-free surgical BCC margins exhibit a tumour promoting phenotype.

  10. High-Speed Rolling of AZ31 Magnesium Alloy Having Different Initial Textures

    Science.gov (United States)

    Onuki, Yusuke; Hara, Kenichiro; Utsunomiya, Hiroshi; Szpunar, Jerzy A.

    2015-02-01

    It is known that magnesium alloys can be rolled up to a large thickness reduction and develop a unique texture when the rolling speed is high (>1000 m/min). In order to understand the texture formation mechanism during high-strain-rate deformation, high-speed rolling of AZ31 magnesium alloy samples having different initial textures was conducted. The main components of the textures after the rolling were the RD-split basal, which consisted of 10°-20° inclining basal poles from the normal direction toward the rolling direction of the sheet, regardless of the different initial textures. With preheating at 473 K, all the samples were rolled without cracking while all were cracked when preheating was not applied. The optical micrographs and EBSD measurements showed a significant amount of twins and the cracks that developed along the shear bands consisted with laminated twins. Based on the texture simulation using the visco-plastic self-consistent model, it is concluded that the rapid development of the RD-split basal component from the initial basal alignment along the transverse direction was attributable to the tension twinning, The effect of the initial texture on the crack formation can be explained by the activation of the twinning system.

  11. Centrioles to basal bodies in the spermiogenesis of Mastotermes darwiniensis (Insecta, Isoptera).

    Science.gov (United States)

    Riparbelli, Maria Giovanna; Callaini, Giuliano; Mercati, David; Hertel, Horst; Dallai, Romano

    2009-05-01

    In addition to their role in centrosome organization, the centrioles have another distinct function as basal bodies for the formation of cilia and flagella. Centriole duplication has been reported to require two alternate assembly pathways: template or de novo. Since spermiogenesis in the termite Mastotermes darwiniensis lead to the formation of multiflagellate sperm, this process represents a useful model system in which to follow basal body formation and flagella assembly. We present evidence of a possible de novo pathway for basal body formation in the differentiating germ cell. This cell also contains typical centrosomal proteins, such as centrosomin, pericentrin-like protein, gamma-tubulin, that undergo redistribution as spermatid differentiation proceeds. The spermatid centrioles are long structures formed by nine doublet rather than triplet microtubules provided with short projections extending towards the surrounding cytoplasm and with links between doublets. The sperm basal bodies are aligned in parallel beneath the nucleus. They consist of long regions close to the nucleus showing nine doublets in a cartwheel array devoid of any projections; on the contrary, the short region close to the plasma membrane, where the sperm flagella emerge, is characterized by projections similar to those observed in the centrioles linking the basal body to the plasma membrane. It is hypothesized that this appearance is in connection with the centriole elongation and further with the flagellar axonemal organization. Microtubule doublets of sperm flagellar axonemes are provided with outer dynein arms, while inner arms are rarely visible. (c) 2009 Wiley-Liss, Inc.

  12. Dissociating basal forebrain and medial temporal amnesic syndromes: insights from classical conditioning.

    Science.gov (United States)

    Myer, Catherine E; Bryant, Deborah; DeLuca, John; Gluck, Mark A

    2002-01-01

    In humans, anterograde amnesia can result from damage to the medial temporal (MT) lobes (including hippocampus), as well as to other brain areas such as basal forebrain. Results from animal classical conditioning studies suggest that there may be qualitative differences in the memory impairment following MT vs. basal forebrain damage. Specifically, delay eyeblink conditioning is spared after MT damage in animals and humans, but impaired in animals with basal forebrain damage. Recently, we have likewise shown delay eyeblink conditioning impairment in humans with amnesia following anterior communicating artery (ACoA) aneurysm rupture, which damages the basal forebrain. Another associative learning task, a computer-based concurrent visual discrimination, also appears to be spared in MT amnesia while ACoA amnesics are slower to learn the discriminations. Conversely, animal and computational models suggest that, even though MT amnesics may learn quickly, they may learn qualitatively differently from controls, and these differences may result in impaired transfer when familiar information is presented in novel combinations. Our initial data suggests such a two-phase learning and transfer task may provide a double dissociation between MT amnesics (spared initial learning but impaired transfer) and ACoA amnesics (slow initial learning but spared transfer). Together, these emerging data suggest that there are subtle but dissociable differences in the amnesic syndrome following damage to the MT lobes vs. basal forebrain, and that these differences may be most visible in non-declarative tasks such as eyeblink classical conditioning and simple associative learning.

  13. Novel signal-dependent filter bank method for identification of multiple basal ganglia nuclei in Parkinsonian patients

    Science.gov (United States)

    Pinzon-Morales, R. D.; Orozco-Gutierrez, A. A.; Castellanos-Dominguez, G.

    2011-06-01

    Microelectrode recordings are a valuable tool for assisting localization targets during deep brain stimulation procedures in Parkinson's disease neurosurgery. Attempts to automate and standardize this process have been limited by variability in patient neurophysiology and strong dynamics of microelectrode recordings. In this paper, a methodology for the identification of basal ganglia nuclei is presented that is based on a signal-dependent filter bank method using microelectrode recordings. The method is a customized realization of the discrete wavelet transform via the lifting scheme that is optimally tuned by genetic algorithms. Using this method, unique mother wavelet functions that exhibit an adaptable spectrum to the microelectrode recording dynamic are generated. Additionally, by extracting morphological features from the space-transformed microelectrode recording, it is possible to integrate them into three-dimensional (3D) feature spaces with maximum class separability. Finally, high discriminant feature spaces are fed into basic classifiers to recognize up to four basal nuclei. Comparison with several existing wavelets highlights the characteristics of new mother wavelets. Additionally, classification results show that identification of addressed nuclei in the basal ganglia can be performed with 95% confidence.

  14. Quantitative expression analysis of selected transcription factors in pavement, basal and trichome cells of mature leaves from Arabidopsis thaliana.

    Science.gov (United States)

    Schliep, Martin; Ebert, Berit; Simon-Rosin, Ulrike; Zoeller, Daniela; Fisahn, Joachim

    2010-05-01

    Gene expression levels of several transcription factors from Arabidopsis thaliana that were described previously to be involved in leaf development and trichome formation were analysed in trichome, basal and pavement cells of mature leaves. Single cell samples of these three cells types were collected by glass micro-capillaries. Real-time reverse transcription (RT)-PCR was used to analyse expression patterns of the following transcription factors: MYB23, MYB55, AtHB1, FILAMENTOUS FLOWER (FIL)/YABBY1 (YAB1), TRIPTYCHON (TRY) and CAPRICE (CPC). A difference in the expression patterns of TRY and CPC was revealed. Contrary to the CPC expression pattern, no transcripts of TRY could be detected in pavement cells. FIL/YAB1 was exclusively expressed in trichome cells. AtHB1 was highly expressed throughout all three cell types. MYB55 was higher expressed in basal cells than in trichome and pavement cells. MYB23 showed a pattern of low expression in pavement cells, medium in basal cells and high expression in trichomes. Expression patterns obtained by single cell sampling and real-time RT-PCR were compared to promoter GUS fusions of the selected transcription factors. Therefore, we regenerated two transgenic Arabidopsis lines that expressed the GUS reporter gene under control of the promoters of MYB55 and YAB1. In conclusion, despite their function in leaf morphogenesis, all six transcription factors were detected in mature leaves. Furthermore, single cell sampling and promoter GUS staining patterns demonstrated the predominant presence of MYB55 in basal cells as compared to pavement cells and trichomes.

  15. Sp1 and CREB regulate basal transcription of the human SNF2L gene

    International Nuclear Information System (INIS)

    Xia Yu; Jiang Baichun; Zou Yongxin; Gao Guimin; Shang Linshan; Chen Bingxi; Liu Qiji; Gong Yaoqin

    2008-01-01

    Imitation Switch (ISWI) is a member of the SWI2/SNF2 superfamily of ATP-dependent chromatin remodelers, which are involved in multiple nuclear functions, including transcriptional regulation, replication, and chromatin assembly. Mammalian genomes encode two ISWI orthologs, SNF2H and SNF2L. In order to clarify the molecular mechanisms governing the expression of human SNF2L gene, we functionally examined the transcriptional regulation of human SNF2L promoter. Reporter gene assays demonstrated that the minimal SNF2L promoter was located between positions -152 to -86 relative to the transcription start site. In this region we have identified a cAMP-response element (CRE) located at -99 to -92 and a Sp1-binding site at -145 to -135 that play a critical role in regulating basal activity of human SNF2L gene, which were proven by deletion and mutation of specific binding sites, EMSA, and down-regulating Sp1 and CREB via RNAi. This study provides the first insight into the mechanisms that control basal expression of human SNF2L gene

  16. Salicylic acid regulates basal resistance to Fusarium head blight in wheat.

    Science.gov (United States)

    Makandar, Ragiba; Nalam, Vamsi J; Lee, Hyeonju; Trick, Harold N; Dong, Yanhong; Shah, Jyoti

    2012-03-01

    Fusarium head blight (FHB) is a destructive disease of cereal crops such as wheat and barley. Previously, expression in wheat of the Arabidopsis NPR1 gene (AtNPR1), which encodes a key regulator of salicylic acid (SA) signaling, was shown to reduce severity of FHB caused by Fusarium graminearum. It was hypothesized that SA signaling contributes to wheat defense against F. graminearum. Here, we show that increased accumulation of SA in fungus-infected spikes correlated with elevated expression of the SA-inducible pathogenesis-related 1 (PR1) gene and FHB resistance. In addition, FHB severity and mycotoxin accumulation were curtailed in wheat plants treated with SA and in AtNPR1 wheat, which is hyper-responsive to SA. In support of a critical role for SA in basal resistance to FHB, disease severity was higher in wheat expressing the NahG-encoded salicylate hydroxylase, which metabolizes SA. The FHB-promoting effect of NahG was overcome by application of benzo (1,2,3), thiadiazole-7 carbothioic acid S-methyl ester, a synthetic functional analog of SA, thus confirming an important role for SA signaling in basal resistance to FHB. We further demonstrate that jasmonate signaling has a dichotomous role in wheat interaction with F. graminearum, constraining activation of SA signaling during early stages of infection and promoting resistance during the later stages of infection.

  17. Giant basal cell carcinoma of the face: surgical management and challenges for reconstruction.

    Science.gov (United States)

    Maimaiti, A; Mijiti, A; Yarbag, A; Moming, A

    2016-02-01

    Giant basal cell carcinoma, in which the tumour measures 5 cm or greater in diameter, is a very rare skin malignancy that accounts for less than 1 per cent of all basal cell tumours. Very few studies have reported on the incidence, resection and reconstruction of this lesion worldwide. In total, 17 patients with giant basal cell carcinoma of the head and neck region underwent surgical excision and reconstruction at our hospital. Medical charts were retrospectively reviewed and analysed. The lesion was usually in the forehead, eyelid, lips or nasal-cheek region. The greatest diameter ranged from 5 to 11 cm, with 5-6 cm being the most common size at the time of presentation. All patients had their tumour resected and reconstructed in a single-stage procedure, mostly with a local advancement flap, and with no post-operative flap failure. Giant basal cell carcinoma of the head and neck can be successfully treated with a local flap in a single-stage approach.

  18. Evaluation of the long-term cost-effectiveness of IDegLira versus liraglutide added to basal insulin for patients with type 2 diabetes failing to achieve glycemic control on basal insulin in the USA.

    Science.gov (United States)

    Hunt, B; Mocarski, M; Valentine, W J; Langer, J

    2017-07-01

    IDegLira, a fixed ratio combination of insulin degludec and glucagon-like peptide-1 receptor agonist liraglutide, utilizes the complementary mechanisms of action of these two agents to improve glycemic control with low risk of hypoglycemia and avoidance of weight gain. The aim of the present analysis was to assess the long-term cost-effectiveness of IDegLira vs liraglutide added to basal insulin, for patients with type 2 diabetes not achieving glycemic control on basal insulin in the US setting. Projections of lifetime costs and clinical outcomes were made using the IMS CORE Diabetes Model. Treatment effect data for patients receiving IDegLira and liraglutide added to basal insulin were modeled based on the outcomes of a published indirect comparison, as no head-to-head clinical trial data is currently available. Costs were accounted in 2015 US dollars ($) from a healthcare payer perspective. IDegLira was associated with small improvements in quality-adjusted life expectancy compared with liraglutide added to basal insulin (8.94 vs 8.91 discounted quality-adjusted life years [QALYs]). The key driver of improved clinical outcomes was the greater reduction in glycated hemoglobin associated with IDegLira. IDegLira was associated with mean costs savings of $17,687 over patient lifetimes vs liraglutide added to basal insulin, resulting from lower treatment costs and cost savings as a result of complications avoided. The present long-term modeling analysis found that IDegLira was dominant vs liraglutide added to basal insulin for patients with type 2 diabetes failing to achieve glycemic control on basal insulin in the US, improving clinical outcomes and reducing direct costs.

  19. Behavioural effects of basal ganglia rho-kinase inhibition in the unilateral 6-hydroxydopamine rat model of Parkinson's disease.

    Science.gov (United States)

    Inan, Salim Yalcin; Soner, Burak Cem; Sahin, Ayse Saide

    2016-08-01

    Parkinson's disease (PD) is one of the most common neurodegenerative disorders, which affects more than six million people in the world. While current available pharmacological therapies for PD in the early stages of the disease usually improve motor symptoms, they cause side effects, such as fluctuations and dyskinesias in the later stages. In this later stage, high frequency deep brain stimulation of the subthalamic nucleus (STN-DBS) is a treatment option which is most successful to treat drug resistant advanced PD. It has previously been demonstrated that activation of Rho/Rho-kinase pathway is involved in the dopaminergic cell degeneration which is one of the main characteristics of PD pathology. In addition, the involvement of this pathway has been suggested in diverse cellular events in the central nervous system; such as epilepsy, anxiety-related behaviors, regulation of dendritic and axonal morphology, antinociception, subarachnoid haemorrhage, spinal cord injury and amyotrophic lateral sclerosis. However, up to date, to our knowledge there are no previous reports showing the beneficial effects of the potent Rho-kinase inhibitor Y-27632 in the 6-hydroxydopamine (6-OHDA) rat model of PD. Therefore, in the present study, we investigated the behavioural effects of basal ganglia Y-27632 microinjections in this PD model. Our results indicated that basal ganglia Y-27632 microinjections significantly decreased the number of contralateral rotations-induced by apomorphine, significantly increased line crossings in the open-field test, contralateral forelimb use in the limb-use asymmetry test and contralateral tape playing time in the somatosensory asymmetry test, which may suggest that Y-27632 could be a potentially active antiparkinsonian agent.

  20. Localization of Basal Ganglia and Thalamic Damage in Dyskinetic Cerebral Palsy.

    Science.gov (United States)

    Aravamuthan, Bhooma R; Waugh, Jeff L

    2016-01-01

    Dyskinetic cerebral palsy affects 15%-20% of patients with cerebral palsy. Basal ganglia injury is associated with dyskinetic cerebral palsy, but the patterns of injury within the basal ganglia predisposing to dyskinetic cerebral palsy are unknown, making treatment difficult. For example, deep brain stimulation of the globus pallidus interna improves dystonia in only 40% of patients with dyskinetic cerebral palsy. Basal ganglia injury heterogeneity may explain this variability. To investigate this, we conducted a qualitative systematic review of basal ganglia and thalamic damage in dyskinetic cerebral palsy. Reviews and articles primarily addressing genetic or toxic causes of cerebral palsy were excluded yielding 22 studies (304 subjects). Thirteen studies specified the involved basal ganglia nuclei (subthalamic nucleus, caudate, putamen, globus pallidus, or lentiform nuclei, comprised by the putamen and globus pallidus). Studies investigating the lentiform nuclei (without distinguishing between the putamen and globus pallidus) showed that all subjects (19 of 19) had lentiform nuclei damage. Studies simultaneously but independently investigating the putamen and globus pallidus also showed that all subjects (35 of 35) had lentiform nuclei damage (i.e., putamen or globus pallidus damage); this was followed in frequency by damage to the putamen alone (70 of 101, 69%), the subthalamic nucleus (17 of 25, 68%), the thalamus (88 of 142, 62%), the globus pallidus (7/35, 20%), and the caudate (6 of 47, 13%). Globus pallidus damage was almost always coincident with putaminal damage. Noting consistent involvement of the lentiform nuclei in dyskinetic cerebral palsy, these results could suggest two groups of patients with dyskinetic cerebral palsy: those with putamen-predominant damage and those with panlenticular damage involving both the putamen and the globus pallidus. Differentiating between these groups could help predict response to therapies such as deep brain