WorldWideScience

Sample records for high basal activity

  1. KDAC8 with High Basal Velocity Is Not Activated by N-Acetylthioureas

    Science.gov (United States)

    2016-01-08

    proteins via a conserved mechanism.[1–3] This cycle of acetylation and deacetylation has been linked to many biological processes , including development...our standard method. To determine if this lack of activation was independent of our enzyme purification process , we performed the same experiments with...Identify Endogenous Substrates of “Histone” Deacetylase 8. ACS Chem Biol. 2014; 2014: 2210–2216. doi: 10.1021/cb500492r 21. Decroos C, Bowman CM, Moser J

  2. The non-active stellar chromosphere: Ca II basal flux

    Science.gov (United States)

    Pérez Martínez, M. I.; Schröder, K.-P.; Hauschildt, P.

    2014-11-01

    We analyse high-resolution, high-s/n European Southern Observatories (ESO)-archive spectra (from UVES, the UV echelle spectrograph) of 76 inactive or modestly active stars of spectral type G to M, main sequence and giants. Using PHOENIX model photospheres with Ca II K lines that match the observed line profiles, we (i) revise the effective temperatures, (ii) obtain a precise surface flux scale for each star and (iii) directly determine the exact surface fluxes of each Ca II K chromospheric emission with respect to the photospheric line profile. We find that our stellar sample exhibits a lower boundary to its chromospheric surface flux distribution with an unprecedented definition. From a subsample of the 25 least active stars, we obtain a simple empirical formula for the basal Ca II flux as a function of effective temperature: log {F^basal_{Ca II(H+K)}} = 7.05(± 0.31) log {T_eff} - 20.86(± 1.15). This is in good agreement with the Mg II basal flux. In a direct comparison with the large body of Mt Wilson S-measurements of the chromospheric Ca II emission and its well-defined cut-off, excellent agreement is achieved as well. A new result, however, is the small scatter of the least active star's fluxes about the basal flux. It is about 25 per cent and equals the residual uncertainties of our approach. At the same time, we do not find any evidence for a gravity dependence within these limits. This strongly confirms the basal flux as a well-defined and universal phenomenon, which characterizes every inactive chromosphere.

  3. Tumor initiating but differentiated luminal-like breast cancer cells are highly invasive in the absence of basal-like activity

    DEFF Research Database (Denmark)

    Kim, Jiyoung; Villadsen, René; Sørlie, Therese

    2012-01-01

    The majority of human breast cancers exhibit luminal epithelial differentiation. However, most aggressive behavior, including invasion and purported cancer stem cell activity, are considered characteristics of basal-like cells. We asked the following questions: Must luminal-like breast cancer cells...... by gene expression, mammosphere formation and lineage markers. Luminal-like cells without basal-like traits, surprisingly, were fully capable of initiating invasive tumors in NOD SCID gamma (NSG) mice. In fact, these phenotypically pure luminal-like cells generated larger and more invasive tumors than...

  4. 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

  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. 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.

  7. Auditory cortex basal activity modulates cochlear responses in chinchillas.

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    Alex León

    Full Text Available BACKGROUND: The auditory efferent system has unique neuroanatomical pathways that connect the cerebral cortex with sensory receptor cells. Pyramidal neurons located in layers V and VI of the primary auditory cortex constitute descending projections to the thalamus, inferior colliculus, and even directly to the superior olivary complex and to the cochlear nucleus. Efferent pathways are connected to the cochlear receptor by the olivocochlear system, which innervates outer hair cells and auditory nerve fibers. The functional role of the cortico-olivocochlear efferent system remains debated. We hypothesized that auditory cortex basal activity modulates cochlear and auditory-nerve afferent responses through the efferent system. METHODOLOGY/PRINCIPAL FINDINGS: Cochlear microphonics (CM, auditory-nerve compound action potentials (CAP and auditory cortex evoked potentials (ACEP were recorded in twenty anesthetized chinchillas, before, during and after auditory cortex deactivation by two methods: lidocaine microinjections or cortical cooling with cryoloops. Auditory cortex deactivation induced a transient reduction in ACEP amplitudes in fifteen animals (deactivation experiments and a permanent reduction in five chinchillas (lesion experiments. We found significant changes in the amplitude of CM in both types of experiments, being the most common effect a CM decrease found in fifteen animals. Concomitantly to CM amplitude changes, we found CAP increases in seven chinchillas and CAP reductions in thirteen animals. Although ACEP amplitudes were completely recovered after ninety minutes in deactivation experiments, only partial recovery was observed in the magnitudes of cochlear responses. CONCLUSIONS/SIGNIFICANCE: These results show that blocking ongoing auditory cortex activity modulates CM and CAP responses, demonstrating that cortico-olivocochlear circuits regulate auditory nerve and cochlear responses through a basal efferent tone. The diversity of the

  8. Anhedonia in the psychosis risk syndrome: associations with social impairment and basal orbitofrontal cortical activity

    OpenAIRE

    Cressman, Victoria L.; Schobel, Scott A.; Steinfeld, Sara; Ben-David, Shelly; Judy L. Thompson; Small, Scott A.; Moore, Holly; Corcoran, Cheryl M.

    2015-01-01

    Background/Objectives: Anhedonia is associated with poor social function in schizophrenia. Here, we examined this association in individuals at clinical high risk (CHR) for schizophrenia and related psychotic disorders, taking into account social anxiety. We then explored correlations between anhedonia and basal metabolic activity in selected forebrain regions implicated in reward processing. Methods: In 62 CHR individuals and 37 healthy controls, we measured social adjustment (Social Adjustm...

  9. Overexpression of Id1 in transgenic mice promotes mammary basal stem cell activity and breast tumorigenesis.

    Science.gov (United States)

    Shin, Dong-Hui; Park, Ji-Hye; Lee, Jeong-Yeon; Won, Hee-Young; Jang, Ki-Seok; Min, Kyueng-Whan; Jang, Si-Hyong; Woo, Jong-Kyu; Oh, Seung Hyun; Kong, Gu

    2015-07-10

    Inhibitor of differentiation/DNA binding (Id)1 is a crucial regulator of mammary development and breast cancer progression. However, its effect on stemness and tumorigenesis in mammary epithelial cells remains undefined. Herein, we demonstrate that Id1 induces mammary tumorigenesis by increasing normal and malignant mammary stem cell (MaSC) activities in transgenic mice. MaSC-enriched basal cell expansion and increased self-renewal and in vivo regenerative capacity of MaSCs are observed in the mammary glands of MMTV-Id1 transgenic mice. Furthermore, MMTV-Id1 mice develop ductal hyperplasia and mammary tumors with highly expressed basal markers. Id1 also increases breast cancer stem cell (CSC) population and activity in human breast cancer lines. Moreover, the effects of Id1 on normal and malignant stem cell activities are mediated by the Wnt/c-Myc pathway. Collectively, these findings provide in vivo genetic evidence of Id1 functions as an oncogene in breast cancer and indicate that Id1 regulates mammary basal stem cells by activating the Wnt/c-Myc pathway, thereby contributing to breast tumor development.

  10. High fat diet promotes prostatic basal-to-luminal differentiation and accelerates initiation of prostate epithelial hyperplasia originated from basal cells

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    Oh-Joon Kwon

    2016-05-01

    Full Text Available Recent lineage tracing studies showed that the prostate basal and luminal cells in adult mice are two independent lineages under the physiological condition, but basal cells are capable of generating luminal progenies during bacterial infection-induced prostatitis. Because acute bacterial infection in human prostate tissues is relatively rare, the disease relevance of the bacterial infection-induced basal-to-luminal differentiation is uncertain. Herein we employ a high fat diet-induced sterile prostate inflammation model to determine whether basal-to-luminal differentiation can be induced by inflammation irrespective of the underlying etiologies. A K14-CreER model and a fluorescent report line are utilized to specifically label basal cells with the green fluorescent protein. We show that high fat diet promotes immune cell infiltration into the prostate tissues and basal-to-luminal differentiation. Increased cell proliferation accompanies basal-to-luminal differentiation, suggesting a concurrent regulation of basal cell proliferation and differentiation. This study demonstrates that basal-to-luminal differentiation can be induced by different types of prostate inflammation evolved with distinct etiologies. Finally, high fat diet also accelerates initiation and progression of prostatic intraepithelial neoplasia that are originated from basal cells with loss-of-function of the tumor suppressor Pten. Because prostate cancer originated from basal cells tends to be invasive, our study also provides an alternative explanation for the association between obesity and aggressive prostate cancer.

  11. Regulation of neuronal gene expression and survival by basal NMDA receptor activity: a role for histone deacetylase 4.

    Science.gov (United States)

    Chen, Yelin; Wang, Yuanyuan; Modrusan, Zora; Sheng, Morgan; Kaminker, Joshua S

    2014-11-12

    Neuronal gene expression is modulated by activity via calcium-permeable receptors such as NMDA receptors (NMDARs). While gene expression changes downstream of evoked NMDAR activity have been well studied, much less is known about gene expression changes that occur under conditions of basal neuronal activity. In mouse dissociated hippocampal neuronal cultures, we found that a broad NMDAR antagonist, AP5, induced robust gene expression changes under basal activity, but subtype-specific antagonists did not. While some of the gene expression changes are also known to be downstream of stimulated NMDAR activity, others appear specific to basal NMDAR activity. The genes altered by AP5 treatment of basal cultures were enriched for pathways related to class IIa histone deacetylases (HDACs), apoptosis, and synapse-related signaling. Specifically, AP5 altered the expression of all three class IIa HDACs that are highly expressed in the brain, HDAC4, HDAC5, and HDAC9, and also induced nuclear accumulation of HDAC4. HDAC4 knockdown abolished a subset of the gene expression changes induced by AP5, and led to neuronal death under long-term tetrodotoxin or AP5 treatment in rat hippocampal organotypic slice cultures. These data suggest that basal, but not evoked, NMDAR activity regulates gene expression in part through HDAC4, and, that HDAC4 has neuroprotective functions under conditions of low NMDAR activity.

  12. Validation of Algorithms for Basal Insulin Rate Reductions in Type 1 Diabetic Patients Practising Physical Activity

    Science.gov (United States)

    2013-04-19

    Type 1 Diabetes With a Subcutaneous Insulin Pump; Adjustment of the Recommended Basal Insulin Flow Rate in the Event of Physical Activity; Adjustment of the Recommended Prandial Insulin in the Event of Physical Activity

  13. 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

    Ice deformation and basal motion characterize the dynamical behavior of the Greenland ice sheet (GrIS). We evaluate the contribution of basal motion from ice deformation measurements in boreholes drilled to the bed at two sites in the western marginal zone of the GrIS. We find a sustained high am...

  14. 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

    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...... agonist. In a hypothalamic cell line that endogenously expresses the ghrelin receptor, we observed high basal activity of the cAMP response element binding protein, an important signaling transduction pathway for appetite regulation. The activation was further increased by ghrelin administration...... and decreased by administration of the inverse agonist. It is suggested that the high constitutive signaling activity is important for the in vivo function of the ghrelin receptor in the control of food intake and body weight....

  15. 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.

  16. [The changes of basal brain electric activity in patients with epilepsy after callosotomy].

    Science.gov (United States)

    Beĭn, B N; Dravert, N E; Tatarenko, S A

    2008-01-01

    Short-term and long-term outcomes of basal brain activity were estimated in 20 epileptic patients with a medical history of callosotomy. Patients with malignant courses selected for callosotomy retained the high capacity of cerebral electric activity after surgery. In spite of limitations of bilateral synchronized irradiation of electric discharges in the brain, patients had the high power of cerebral electric genesis. A clinical study revealed the decrease of the number of seizures and their severity in patients who underwent the surgery. Thus, callosotomy plays only a palliative role in epileptic processes. Of primary importance is individual selection of anti-epileptic drugs to support cell mechanisms of epilepsy and improvement of treatment outcomes.

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  18. Kv3-Like Potassium Channels Are Required for Sustained High-Frequency Firing in Basal Ganglia Output Neurons

    OpenAIRE

    Ding, Shengyuan; Matta, Shannon G.; Zhou, Fu-Ming

    2010-01-01

    The GABA projection neurons in the substantial nigra pars reticulata (SNr) are key output neurons of the basal ganglia motor control circuit. These neurons fire sustained high-frequency, short-duration spikes that provide a tonic inhibition to their targets and are critical to movement control. We hypothesized that a robust voltage-activated K+ conductance that activates quickly and resists inactivation is essential to the remarkable fast-spiking capability in these neurons. Semi-quantitative...

  19. Neuronal activity (c-Fos delineating interactions of the cerebral cortex and basal ganglia

    Directory of Open Access Journals (Sweden)

    Mei-Hong eQiu

    2014-03-01

    Full Text Available The cerebral cortex and basal ganglia (BG form a neural circuit that is disrupted in disorders such as Parkinson’s disease. We found that neuronal activity (c-Fos in the BG followed cortical activity, i.e., high in arousal state and low in sleep state. To determine if cortical activity is necessary for BG activity, we administered atropine to rats to induce a dissociative state resulting in slow-wave EEG but hyperactive motor behaviors. Atropine blocked c-Fos expression in the cortex and BG, despite high c-Fos expression in the sub-cortical arousal neuronal groups and thalamus, indicating that cortical activity is required for BG activation. To identify which glutamate receptors in the BG that mediate cortical inputs, we injected ketamine (NMDA receptor antagonist and 6-cyano-nitroquinoxaline-2, 3-dione (CNQX, a non-NMDA receptor antagonist. Systemic ketamine and CNQX administration revealed that NMDA receptors mediated subthalamic nucleus (STN input to internal globus pallidus (GPi and substantia nigra pars reticulata (SNr, while non-NMDA receptor mediated cortical input to the STN. Both types of glutamate receptors were involved in mediating cortical input to the striatum. Dorsal striatal (caudoputamen, CPu dopamine depletion by 6-hydroxydopamine resulted in reduced activity of the CPu, globus pallidus externa (GPe, and STN but increased activity of the GPi, SNr and putative layer V neurons in the motor cortex. Our results reveal that the cortical activity is necessary for BG activity and clarifies the pathways and properties of the BG-cortical network and their putative role in the pathophysiology of BG disorders.

  20. 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...

  1. Cholesterol-mediated activation of P-glycoprotein: distinct effects on basal and drug-induced ATPase activities.

    Science.gov (United States)

    Belli, Sara; Elsener, Priska M; Wunderli-Allenspach, Heidi; Krämer, Stefanie D

    2009-05-01

    Cholesterol promotes basal and verapamil-induced ATPase activity of P-glycoprotein (P-gp). We investigated whether these effects are related to each other and to the impact of the sterol on bilayer fluidity and verapamil membrane affinity. P-gp was reconstituted in egg-phosphatidylcholine (PhC) liposomes with or without cholesterol, 1,2-dipalmitoyl-phosphatidylcholine (DPPC), alpha-tocopherol (alpha-Toc) or 2,2,5,7,8-pentamethyl-6-chromanol (PMC). Basal and verapamil-induced ATPase activities were studied with an enzymatic assay. Membrane fluidity was characterized with diphenyl-hexatriene anisotropy measurements and membrane affinity by equilibrium dialysis. DPPC (70% mol/mol) decreased the fluidity of PhC bilayers to the same level as 20% cholesterol. PMC (20%) and alpha-Toc (20%) decreased the fluidity to lesser extents. alpha-Toc and PMC, but not DPPC increased the verapamil membrane affinity. While 20% cholesterol strikingly enhanced the basal ATPase activity, none of the other constituents had a similar effect. In contrast, verapamil stimulation of P-gp ATPase activity was not only enabled by cholesterol but also by alpha-Toc and DPPC. PMC had no effect. In conclusion, cholesterol exerts distinct effects on basal and verapamil-induced ATPase activity. The influence on basal ATPase activity is sterol-specific while its effect on verapamil-induced ATPase activity is unspecific and not related to its influence on membrane fluidity and on verapamil membrane affinity.

  2. Decreased basal ganglia activation in subjects with chronic fatigue syndrome: association with symptoms of fatigue.

    Directory of Open Access Journals (Sweden)

    Andrew H Miller

    Full Text Available Reduced basal ganglia function has been associated with fatigue in neurologic disorders, as well as in patients exposed to chronic immune stimulation. Patients with chronic fatigue syndrome (CFS have been shown to exhibit symptoms suggestive of decreased basal ganglia function including psychomotor slowing, which in turn was correlated with fatigue. In addition, CFS patients have been found to exhibit increased markers of immune activation. In order to directly test the hypothesis of decreased basal ganglia function in CFS, we used functional magnetic resonance imaging to examine neural activation in the basal ganglia to a reward-processing (monetary gambling task in a community sample of 59 male and female subjects, including 18 patients diagnosed with CFS according to 1994 CDC criteria and 41 non-fatigued healthy controls. For each subject, the average effect of winning vs. losing during the gambling task in regions of interest (ROI corresponding to the caudate nucleus, putamen, and globus pallidus was extracted for group comparisons and correlational analyses. Compared to non-fatigued controls, patients with CFS exhibited significantly decreased activation in the right caudate (p = 0.01 and right globus pallidus (p = 0.02. Decreased activation in the right globus pallidus was significantly correlated with increased mental fatigue (r2 = 0.49, p = 0.001, general fatigue (r2 = 0.34, p = 0.01 and reduced activity (r2 = 0.29, p = 0.02 as measured by the Multidimensional Fatigue Inventory. No such relationships were found in control subjects. These data suggest that symptoms of fatigue in CFS subjects were associated with reduced responsivity of the basal ganglia, possibly involving the disruption of projections from the globus pallidus to thalamic and cortical networks.

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

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    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.

  4. Activity of the basal ganglia in Parkinson`s disease estimated by PET

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    Ohye, Chihiro [Gunma Univ., Maebashi (Japan). School of Medicine

    1995-04-01

    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 {sup 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{sub 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.).

  5. High Resolution Ice Surface of the Ross Ice Shelf: Accuracy and Links to Basal Processes

    Science.gov (United States)

    Starke, S. E.

    2015-12-01

    We use airborne laser altimetry data from IcePod and IceBridge to map the surface across the Ross Ice Shelf in Antarctica. Laser altimetry and radar data is analyzed from the IcePod 2014 and 2015 field campaigns as well as IceBridge 2013. Icepod is a multi sensor suite that includes ice penetrating radars, a swath scanning laser, visible and IR cameras as well as GPS mounted on a LC-130. Using shallow ice radar data from both IcePod and IceBridge we identify the base of the ice shelf. Across the shelf we observe distinct areas of high reflectivity in the radar data suggesting basal crevassing. In some regions, the basal reflector is not well defined. Laser altimetry profiles correlate surface morphology with features at the base including basal crevasses and marine ice formed by freezing on to the base of the ice shelf. Building Digital Elevation Models (DEMs) from the laser altimetry data, we investigate the relationship between the surface expressions of these ice shelf dynamics including thickness changes, potential sites of marine ice at the base and basal morphology in regions where a well defined basal reflector does not exist in the radar profiles. We present accuracy of the IcePod laser altimetry dataset using ground control points and GPS grids from Greenland and Antarctica as well as Photogrammetric DEMs. Our laser altimetry analysis resolves sub-meter surface features which, combined with coincident radar, provides a link between basal processes and their surface expressions.

  6. Alzheimer caregiver stress: basal natural killer cell activity, pituitary-adrenal cortical function, and sympathetic tone.

    Science.gov (United States)

    Irwin, M; Hauger, R; Patterson, T L; Semple, S; Ziegler, M; Grant, I

    1997-01-01

    The association between Alzheimer caregiving and natural killer (NK) cell activity and basal plasma levels of adrenocorticotropic hormone (ACTH), cortisol, beta-endorphin, prolactin, epinephrine, norepinephrine, and neuropeptide Y was determined in 100 spousal Alzheimer caregivers and 33 age- and gender-comparable control volunteers upon intake into a study of the psychological and physiologic impact of caregiving. The relationship between these physiologic measures and individual characteristics such as age, gender, medical status, severity of stress, severity of depressive symptoms, and caregiver burden was tested. In addition, the association between NK activity and alterations of the neuroendocrine measures was investigated. As compared to controls, the Alzheimer caregivers had similar levels of NK activity and of basal plasma neuroendocrine hormones and sympathetic measures. While older age and male gender status were associated with increased levels of ACTH, neither medical caseness, severity of life stress, nor severity of depressive symptoms was associated with alterations in any of the multiple physiologic domains. Classification of Alzheimer caregiver burden identified caregivers who were mismatched in terms of the amount of care they were required to provide and the amount of respite time received. The mismatched caregivers had significantly higher basal plasma ACTH but no change in other physiological measures, as compared to non-mismatched caregivers. NK activity was negatively correlated with plasma levels of neuropeptide Y but not with any of the other neuroendocrine measures. Based on this cross-sectional evaluation of NK activity and neuroendocrine and sympathetic measures, we conclude that most Alzheimer caregivers do not show evidence of altered basal physiology.

  7. Basal paravian functional anatomy illuminated by high-detail body outline

    Science.gov (United States)

    Wang, Xiaoli; Pittman, Michael; Zheng, Xiaoting; Kaye, Thomas G.; Falk, Amanda R.; Hartman, Scott A.; Xu, Xing

    2017-01-01

    Body shape is a fundamental expression of organismal biology, but its quantitative reconstruction in fossil vertebrates is rare. Due to the absence of fossilized soft tissue evidence, the functional consequences of basal paravian body shape and its implications for the origins of avians and flight are not yet fully understood. Here we reconstruct the quantitative body outline of a fossil paravian Anchiornis based on high-definition images of soft tissues revealed by laser-stimulated fluorescence. This body outline confirms patagia-bearing arms, drumstick-shaped legs and a slender tail, features that were probably widespread among paravians. Finely preserved details also reveal similarities in propatagial and footpad form between basal paravians and modern birds, extending their record to the Late Jurassic. The body outline and soft tissue details suggest significant functional decoupling between the legs and tail in at least some basal paravians. The number of seemingly modern propatagial traits hint that feathering was a significant factor in how basal paravians utilized arm, leg and tail function for aerodynamic benefit. PMID:28248287

  8. Glucose Enhances Basal or Melanocortin-Induced cAMP-Response Element Activity in Hypothalamic Cells.

    Science.gov (United States)

    Breit, Andreas; Wicht, Kristina; Boekhoff, Ingrid; Glas, Evi; Lauffer, Lisa; Mückter, Harald; Gudermann, Thomas

    2016-07-01

    Melanocyte-stimulating hormone (MSH)-induced activation of the cAMP-response element (CRE) via the CRE-binding protein in hypothalamic cells promotes expression of TRH and thereby restricts food intake and increases energy expenditure. Glucose also induces central anorexigenic effects by acting on hypothalamic neurons, but the underlying mechanisms are not completely understood. It has been proposed that glucose activates the CRE-binding protein-regulated transcriptional coactivator 2 (CRTC-2) in hypothalamic neurons by inhibition of AMP-activated protein kinases (AMPKs), but whether glucose directly affects hypothalamic CRE activity has not yet been shown. Hence, we dissected effects of glucose on basal and MSH-induced CRE activation in terms of kinetics, affinity, and desensitization in murine, hypothalamic mHypoA-2/10-CRE cells that stably express a CRE-dependent reporter gene construct. Physiologically relevant increases in extracellular glucose enhanced basal or MSH-induced CRE-dependent gene transcription, whereas prolonged elevated glucose concentrations reduced the sensitivity of mHypoA-2/10-CRE cells towards glucose. Glucose also induced CRCT-2 translocation into the nucleus and the AMPK activator metformin decreased basal and glucose-induced CRE activity, suggesting a role for AMPK/CRTC-2 in glucose-induced CRE activation. Accordingly, small interfering RNA-induced down-regulation of CRTC-2 expression decreased glucose-induced CRE-dependent reporter activation. Of note, glucose also induced expression of TRH, suggesting that glucose might affect the hypothalamic-pituitary-thyroid axis via the regulation of hypothalamic CRE activity. These findings significantly advance our knowledge about the impact of glucose on hypothalamic signaling and suggest that TRH release might account for the central anorexigenic effects of glucose and could represent a new molecular link between hyperglycaemia and thyroid dysfunction.

  9. Overexpression of Id1 in transgenic mice promotes mammary basal stem cell activity and breast tumorigenesis

    OpenAIRE

    Shin, Dong-Hui; Park, Ji-Hye; Lee, Jeong-Yeon; Won, Hee-Young; Jang, Ki-Seok; MIN, KYUENG-WHAN; Jang, Si-Hyong; Woo, Jong-Kyu; Oh, Seung Hyun; Kong, Gu

    2015-01-01

    Inhibitor of differentiation/DNA binding (Id)1 is a crucial regulator of mammary development and breast cancer progression. However, its effect on stemness and tumorigenesis in mammary epithelial cells remains undefined. Herein, we demonstrate that Id1 induces mammary tumorigenesis by increasing normal and malignant mammary stem cell (MaSC) activities in transgenic mice. MaSC-enriched basal cell expansion and increased self-renewal and in vivo regenerative capacity of MaSCs are observed in th...

  10. Delta-mediated cross-frequency coupling organizes oscillatory activity across the rat cortico-basal ganglia network

    Directory of Open Access Journals (Sweden)

    Jon eLópez-Azcárate

    2013-10-01

    Full Text Available The brain's ability to integrate different behavioral and cognitive processes relies on its capacity to generate neural oscillations in a cooperative and coordinated manner. Cross-frequency coupling (CFC has recently been proposed as one of the mechanisms involved in organizing brain activity. Here we investigated the phase-to-amplitude CFC (PA-CFC patterns of the oscillatory activity in the cortico-basal ganglia network of healthy, freely moving rats. Within-structure analysis detected consistent PA-CFC patterns in the four regions analyzed, with the phase of delta waves modulating the amplitude of activity in the gamma (low-gamma ~50 Hz; high-gamma ~80 Hz and high frequency ranges (high frequency oscillations HFO, ~150 Hz. Between-structure analysis revealed that the phase of delta waves parses the occurrence of transient episodes of coherence in the gamma and high frequency bands across the entire network, providing temporal windows of coherence between different structures. Significantly, this specific spatio-temporal organization was affected by the action of dopaminergic drugs. Taken together, our findings suggest that delta-mediated PA-CFC plays a key role in the organization of local and distant activities in the rat cortico-basal ganglia network by fine-tuning the timing of synchronization events across different structures.

  11. Regulation of Neuronal Gene Expression and Survival by Basal NMDA Receptor Activity: A Role for Histone Deacetylase 4

    OpenAIRE

    Chen, Yelin; Wang, Yuanyuan; Modrusan, Zora; Sheng, Morgan; Kaminker, Joshua S.

    2014-01-01

    Neuronal gene expression is modulated by activity via calcium-permeable receptors such as NMDA receptors (NMDARs). While gene expression changes downstream of evoked NMDAR activity have been well studied, much less is known about gene expression changes that occur under conditions of basal neuronal activity. In mouse dissociated hippocampal neuronal cultures, we found that a broad NMDAR antagonist, AP5, induced robust gene expression changes under basal activity, but subtype-specific antagoni...

  12. Sustained High Basal Motion of the Greenland Ice Sheet Revealed by Borehole Deformation

    Science.gov (United States)

    Ryser, Claudia; Luthi, Martin P.; Andrews, Lauren C.; Hoffman, Matthew, J.; Catania, Ginny A.; Hawley, Robert L.; Neumann, Thomas A.; Kristensen, Steen S.

    2014-01-01

    Ice deformation and basal motion characterize the dynamical behavior of the Greenland ice sheet (GrIS). We evaluate the contribution of basal motion from ice deformation measurements in boreholes drilled to the bed at two sites in the western marginal zone of the GrIS. We find a sustained high amount of basal motion contribution to surface velocity of 44-73 percent in winter, and up to 90 percent 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. This effect necessitates the use of high-order ice-flow models, not only in regions of fast-flowing ice streams but in all temperate-based areas of the GrIS. The agreement between modeled and measured deformation rates confirms that the recommended values of the temperature-dependent flow rate factor A are a good choice for ice-sheet models.

  13. 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...... 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......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...

  14. ER stress activates NF-κB by integrating functions of basal IKK activity, IRE1 and PERK.

    Directory of Open Access Journals (Sweden)

    Arvin B Tam

    Full Text Available NF-κB, a transcription factor, becomes activated during the Unfolded Protein Response (UPR, an endoplasmic reticulum (ER stress response pathway. NF-κB is normally held inactive by its inhibitor, IκBα. Multiple cellular pathways activate IKK (IκBα Kinase which phosphorylate IκBα leading to its degradation and NF-κB activation. Here, we find that IKK is required for maximum activation of NF-κB in response to ER stress. However, unlike canonical NFκB activation, IKK activity does not increase during ER stress, but rather the level of basal IKK activity is critical for determining the extent of NF-κB activation. Furthermore, a key UPR initiator, IRE1, acts to maintain IKK basal activity through IRE1's kinase, but not RNase, activity. Inputs from IRE1 and IKK, in combination with translation repression by PERK, another UPR initiator, lead to maximal NF-κB activation during the UPR. These interdependencies have a significant impact in cancer cells with elevated IKK/NF-κB activity such as renal cell carcinoma cells (786-0. Inhibition of IKK by an IKK inhibitor, which significantly decreases NF-κB activity, is overridden by UPR induction, arguing for the importance of considering UPR activation in cancer treatment.

  15. Activity of basal forebrain neurons in the rat during motivated behaviors.

    Science.gov (United States)

    Mink, J W; Sinnamon, H M; Adams, D B

    1983-04-01

    The activity of single neurons in the basal forebrain was recorded in the freely-moving rat with moveable fine-wire electrodes. Neural activity was observed while the water-deprived male rat was exposed to three different types of motivating stimuli that elicit locomotion in a running wheel: an estrous female rat; a drinking tube containing water; and grasping and lifting by the experimenter. The neural activity was also observed when the subject was presented with standardized sensory tests and during single pulse stimulation of other brain structures. A majority of the 76 neurons recorded in the forebrain changed their firing rate during orienting and/or locomotion in general (23 neurons) or during behavior related to only one of the specific motivational contexts: the conspecific female (4 neurons); water (7 neurons); or grasp by the experimenter (8 neurons). Whereas the neurons related to orienting and/or locomotion in general were scattered through various brain structures, those neurons related to specific motivational contexts were concentrated in specific areas: the sexually dimorphic nucleus of the medial preoptic area (conspecific female); lateral septum (water); and lateral preoptic area (water and grasp). The present results, although based on relatively few neurons, are consonant with results of research using other techniques. This indicates that analyses at the level of the single neuron promise to be useful for understanding the role of the basal forebrain in motivational systems.

  16. 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

  17. 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.

  18. 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.

  19. Characterization of basal-prismatic interface of ? twin in deformed titanium by high-resolution transmission electron microscopy

    Science.gov (United States)

    Sun, Q.; Zhang, X. Y.; Tu, J.; Ren, Y.; Qin, H.; Liu, Q.

    2015-03-01

    Disconnections in the basal-prismatic (BP) interfaces of ? twin have been investigated by many computer simulations. In this paper, we report experimentally that the disconnection in the BP interface of ? twin in deformed titanium can be observed by high-resolution TEM (HRTEM). This disconnection can be characterized as ? using a coherent dichromatic complex. Correspondingly, the migration process of the basal-prismatic plane resulting from ? glide is described.

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

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    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

  1. Stress-and Pathogen-Induced Arabidopsis WRKY48 is a Transcriptional Activator that Represses Plant Basal Defense

    Institute of Scientific and Technical Information of China (English)

    Deng-Hui Xing; Zi-Bing Lai; Zu-Yu Zheng; K. M. Vinod; Bao-Fang Fan; Zhi-Xiang Chen

    2008-01-01

    Plant WRKY transcription factors can function as either positive or negative regulators of plant basal disease resistance. Arabidopsis WRKY48 is induced by mechanical and/or osmotic stress due to infiltration and pathogen infection and, therefore, may play a role in plant defense responses. WRKY48 is localized to the nucleus, recognizes the TrGACC Wbox sequence with a high affinity in vitro and functions in plant cells as a strong transcriptional activator. To determine the biological functions directly, we have isolated loss-of-function T-DNA insertion mutants and generated gain-of-function transgenic overexpression plants for WRKY48 in Arabidopsis. Growth of a virulent strain of the bacterial pathogen Pseudomonas syringae was decreased in the wrky48T-DNA insertion mutants. The enhanced resistance of the loss-of-function mutants was associated with increased induction of salicylic acid-regulated PR1 by the bacterial pathogen. By contrast, transgenic WRKY48-0verexpressing plants support enhanced growth of P syringae and the enhanced susceptibility was associated with reduced expression of defense-related PR genes. These results suggest that WRKY48 is a negative regulator of PR gene expression and basal resistance to the bacterial pathogen P syringae.

  2. 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.

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

    Directory of Open Access Journals (Sweden)

    Lyudmyla Dorosh

    2014-01-01

    Full Text Available 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.

  4. Research resource: Comparative nuclear receptor atlas: basal and activated peritoneal B-1 and B-2 cells.

    Science.gov (United States)

    Diehl, Cody J; Barish, Grant D; Downes, Michael; Chou, Meng-Yun; Heinz, Sven; Glass, Christopher K; Evans, Ronald M; Witztum, Joseph L

    2011-03-01

    Naïve murine B cells are typically divided into three subsets based on functional and phenotypic characteristics: innate-like B-1 and marginal zone B cells vs. adaptive B-2 cells, also known as follicular or conventional B cells. B-1 cells, the innate-immune-like component of the B cell lineage are the primary source of natural antibodies and have been shown to modulate autoimmune diseases, human B-cell leukemias, and inflammatory disorders such as atherosclerosis. On the other hand, B-2 cells are the principal mediators of the adaptive humoral immune response and represent an important pharmacological target for various conditions including rheumatoid arthritis, lupus erythematosus, and lymphomas. Using the resources of the Nuclear Receptor Signaling Atlas program, we used quantitative real-time PCR to assess the complement of the 49 murine nuclear receptor superfamily expressed in quiescent and toll-like receptor (TLR)-stimulated peritoneal B-1 and B-2 cells. We report the expression of 24 nuclear receptors in basal B-1 cells and 25 nuclear receptors in basal B-2 cells, with, in some cases, dramatic changes in response to TLR 4 or TLR 2/1 stimulation. Comparative nuclear receptor profiling between B-1 and peritoneal B-2 cells reveals a highly concordant expression pattern, albeit at quantitatively dissimilar levels. We also found that splenic B cells express 23 nuclear receptors. This catalog of nuclear receptor expression in B-1 and B-2 cells provides data to be used to better understand the specific roles of nuclear receptors in B cell function, chronic inflammation, and autoimmune disease.

  5. Concerted action of neuroepithelial basal shrinkage and active epithelial migration ensures efficient optic cup morphogenesis

    Science.gov (United States)

    Sidhaye, Jaydeep; Norden, Caren

    2017-01-01

    Organ formation is a multi-scale event that involves changes at the intracellular, cellular and tissue level. Organogenesis often starts with the formation of characteristically shaped organ precursors. However, the cellular mechanisms driving organ precursor formation are often not clear. Here, using zebrafish, we investigate the epithelial rearrangements responsible for the development of the hemispherical retinal neuroepithelium (RNE), a part of the optic cup. We show that in addition to basal shrinkage of RNE cells, active migration of connected epithelial cells into the RNE is a crucial player in its formation. This cellular movement is driven by progressive cell-matrix contacts and actively translocates prospective RNE cells to their correct location before they adopt neuroepithelial fate. Failure of this migration during neuroepithelium formation leads to ectopic determination of RNE cells and consequently impairs optic cup formation. Overall, this study illustrates how spatiotemporal coordination between morphogenic movements and fate determination critically influences organogenesis. DOI: http://dx.doi.org/10.7554/eLife.22689.001 PMID:28372636

  6. Kv3-like potassium channels are required for sustained high-frequency firing in basal ganglia output neurons.

    Science.gov (United States)

    Ding, Shengyuan; Matta, Shannon G; Zhou, Fu-Ming

    2011-02-01

    The GABA projection neurons in the substantial nigra pars reticulata (SNr) are key output neurons of the basal ganglia motor control circuit. These neurons fire sustained high-frequency, short-duration spikes that provide a tonic inhibition to their targets and are critical to movement control. We hypothesized that a robust voltage-activated K(+) conductance that activates quickly and resists inactivation is essential to the remarkable fast-spiking capability in these neurons. Semi-quantitative RT-PCR (qRT-PCR) analysis on laser capture-microdissected nigral neurons indicated that mRNAs for Kv3.1 and Kv3.4, two key subunits for forming high activation threshold, fast-activating, slow-inactivating, 1 mM tetraethylammonium (TEA)-sensitive, fast delayed rectifier (I(DR-fast)) type Kv channels, are more abundant in fast-spiking SNr GABA neurons than in slow-spiking nigral dopamine neurons. Nucleated patch clamp recordings showed that SNr GABA neurons have a strong Kv3-like I(DR-fast) current sensitive to 1 mM TEA that activates quickly at depolarized membrane potentials and is resistant to inactivation. I(DR-fast) is smaller in nigral dopamine neurons. Pharmacological blockade of I(DR-fast) by 1 mM TEA impaired the high-frequency firing capability in SNr GABA neurons. Taken together, these results indicate that Kv3-like channels mediating fast-activating, inactivation-resistant I(DR-fast) current are critical to the sustained high-frequency firing in SNr GABA projection neurons and hence movement control.

  7. 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.

  8. 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.

  9. High physical fitness is associated with reduction in basal- and exercise-induced inflammation.

    Science.gov (United States)

    Kleiven, Ø; Bjørkavoll-Bergseth, M; Melberg, T; Skadberg, Ø; Bergseth, R; Selvåg, J; Auestad, B; Aukrust, P; Aarsland, T; Ørn, S

    2017-03-17

    C-reactive protein (CRP) increases after strenuous exercise. It has been a concern that prolonged strenuous exercise may be harmful and induce a deleterious inflammatory response. The purpose of this study was to (a) assess and quantify the magnitude of CRP response following an endurance cycling competition in healthy middle-aged recreational cyclists. (b) Identify important determinants of this response. (c) Identify the relationship between CRP, myocardial damage (cardiac Troponin I (cTnI)), and myocardial strain (B-type natriuretic peptide [BNP]). (d) Identify the relationship between CRP and clinical events, defined as utilization of healthcare services or self-reported unusual discomfort. Race time was used as a measure of physical fitness. A total of 97 individuals (43±10 years of age, 74 [76%] males) were assessed prior to and 0, 3, and 24 hours following the 91-km mountain bike race "Nordsjørittet" (Sandnes, Norway, June 2013). There was a highly significant increase in CRP from baseline to 24 hours (0.9 (0.5-1.8) mg/L vs. 11.6 (6.0-17.5) mg/L (median[IQR]), Pfitness was associated with reduction in both basal- and exercise-induced CRP. No adverse relationship was found between high intensity physical exercise, CRP levels, and outcomes.

  10. Cardiac repolarization during hypoglycaemia in type 1 diabetes: impact of basal renin-angiotensin system activity

    DEFF Research Database (Denmark)

    Due-Andersen, Rikke; Høi-Hansen, Thomas; Larroude, Charlotte Ellen;

    2008-01-01

    activity affects cardiac repolarization during hypoglycaemia, thereby potentially carrying prognostic information on risk of the 'dead-in-bed syndrome'. METHODS AND RESULTS: Nine subjects with high RAS activity and nine subjects with low RAS activity were subjected to single-blinded placebo...

  11. The candidate histocompatibility locus of a Basal chordate encodes two highly polymorphic proteins.

    Directory of Open Access Journals (Sweden)

    Marie L Nydam

    Full Text Available The basal chordate Botryllus schlosseri undergoes a natural transplantation reaction governed by a single, highly polymorphic locus called the fuhc. Our initial characterization of this locus suggested it encoded a single gene alternatively spliced into two transcripts: a 555 amino acid-secreted form containing the first half of the gene, and a full-length, 1008 amino acid transmembrane form, with polymorphisms throughout the ectodomain determining outcome. We have now found that the locus encodes two highly polymorphic genes which are separated by a 227 bp intergenic region: first, the secreted form as previously described, and a second gene encoding a 531 amino acid membrane-bound gene containing three extracellular immunoglobulin domains. While northern blotting revealed only these two mRNAs, both PCR and mRNA-seq detect a single capped and polyadenylated transcript that encodes processed forms of both genes linked by the intergenic region, as well as other transcripts in which exons of the two genes are spliced together. These results might suggest that the two genes are expressed as an operon, during which both genes are co-transcribed and then trans-spliced into two separate messages. This type of transcriptional regulation has been described in tunicates previously; however, the membrane-bound gene does not encode a typical Splice Leader (SL sequence at the 5' terminus that usually accompanies trans-splicing. Thus, the presence of stable transcripts encoding both genes may suggest a novel mechanism of regulation, or conversely may be rare but stable transcripts in which the two mRNAs are linked due to a small amount of read-through by RNA polymerase. Both genes are highly polymorphic and co-expressed on tissues involved in histocompatibility. In addition, polymorphisms on both genes correlate with outcome, although we have found a case in which it appears that the secreted form may be major allorecognition determinant.

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

    NARCIS (Netherlands)

    Gorissen, S.H.; Horstman, Astrid; Franssen, Rinske; Kouw, I.W.; Wall, B.T.; Burd, N.A.; Groot, de C.P.G.M.; Loon, van L.J.C.

    2017-01-01

    Background: 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

  13. Nitric oxide activates leak K+ currents in the presumed cholinergic neuron of basal forebrain.

    Science.gov (United States)

    Kang, Youngnam; Dempo, Yoshie; Ohashi, Atsuko; Saito, Mitsuru; Toyoda, Hiroki; Sato, Hajime; Koshino, Hisashi; Maeda, Yoshinobu; Hirai, Toshihiro

    2007-12-01

    Learning and memory are critically dependent on basal forebrain cholinergic (BFC) neuron excitability, which is modulated profoundly by leak K(+) channels. Many neuromodulators closing leak K(+) channels have been reported, whereas their endogenous opener remained unknown. We here demonstrate that nitric oxide (NO) can be the endogenous opener of leak K(+) channels in the presumed BFC neurons. Bath application of 1 mM S-nitroso-N-acetylpenicillamine (SNAP), an NO donor, induced a long-lasting hyperpolarization, which was often interrupted by a transient depolarization. Soluble guanylyl cyclase inhibitors prevented SNAP from inducing hyperpolarization but allowed SNAP to cause depolarization, whereas bath application of 0.2 mM 8-bromoguanosine-3',5'-cyclomonophosphate (8-Br-cGMP) induced a similar long-lasting hyperpolarization alone. These observations indicate that the SNAP-induced hyperpolarization and depolarization are mediated by the cGMP-dependent and -independent processes, respectively. When examined with the ramp command pulse applied at -70 mV under the voltage-clamp condition, 8-Br-cGMP application induced the outward current that reversed at K(+) equilibrium potential (E(K)) and displayed Goldman-Hodgkin-Katz rectification, indicating the involvement of voltage-independent K(+) current. By contrast, SNAP application in the presumed BFC neurons either dialyzed with the GTP-free internal solution or in the presence of 10 muM Rp-8-bromo-beta-phenyl-1,N(2)-ethenoguanosine 3',5'-cyclic monophosphorothioate sodium salt, a protein kinase G (PKG) inhibitor, induced the inward current that reversed at potentials much more negative than E(K) and close to the reversal potential of Na(+)-K(+) pump current. These observations strongly suggest that NO activates leak K(+) channels through cGMP-PKG-dependent pathway to markedly decrease the excitability in BFC neurons, while NO simultaneously causes depolarization by the inhibition of Na(+)-K(+) pump through ATP

  14. Probing the Role of Medication, DBS Electrode Position, and Antidromic Activation on Impulsivity Using a Computational Model of Basal Ganglia.

    Science.gov (United States)

    Mandali, Alekhya; Chakravarthy, V Srinivasa

    2016-01-01

    Everyday, we encounter situations where available choices are nearly equally rewarding (high conflict) calling for some tough decision making. Experimental recordings showed that the activity of Sub Thalamic Nucleus (STN) increases during such situations providing the extra time needed to make the right decision, teasing apart the most rewarding choice from the runner up closely trailing behind. This prolonged deliberation necessary for decision making under high conflict was absent in Parkinson's disease (PD) patients who underwent Deep Brain Stimulation (DBS) surgery of STN. In an attempt to understand the underlying cause of such adverse response, we built a 2D spiking network model (50 × 50 lattice) of Basal ganglia incorporating the key nuclei. Using the model we studied the Probabilistic learning task (PLT) in untreated, treated (L-Dopa and Dopamine Agonist) and STN-DBS PD conditions. Based on the experimental observation that dopaminergic activity is analogous to temporal difference (TD) and induces cortico-striatal plasticity, we introduced learning in the cortico-striatal weights. The results show that healthy and untreated conditions of PD model were able to more or less equally select (avoid) the rewarding (punitive) choice, a behavior that was absent in treated PD condition. The time taken to select a choice in high conflict trials was high in normal condition, which is in agreement with experimental results. The treated PD (Dopamine Agonist) patients made impulsive decisions (small reaction time) which in turn led to poor performance. The underlying cause of the observed impulsivity in DBS patients was studied in the model by (1) varying the electrode position within STN, (2) causing antidromic activation of GPe neurons. The effect of electrode position on reaction time was analyzed by studying the activity of STN neurons where, a decrease in STN neural activity was observed for certain electrode positions. We also observed that a higher antidromic

  15. Fractional laser-mediated photodynamic therapy of high-risk basal cell carcinomas

    DEFF Research Database (Denmark)

    Haak, C S; Togsverd-Bo, K; Thaysen-Petersen, D

    2015-01-01

    BACKGROUND: Photodynamic therapy (PDT) is approved for selected nodular basal cell carcinomas (nBCC) but efficacy is reduced for large and thick tumours. Ablative fractional lasers (AFXL) facilitate uptake of methyl aminolaevulinate (MAL) and may thus improve PDT outcome. OBJECTIVES: To evaluate...

  16. Methylphenidate exposure induces dopamine neuron loss and activation of microglia in the basal ganglia of mice.

    Directory of Open Access Journals (Sweden)

    Shankar Sadasivan

    Full Text Available BACKGROUND: Methylphenidate (MPH is a psychostimulant that exerts its pharmacological effects via preferential blockade of the dopamine transporter (DAT and the norepinephrine transporter (NET, resulting in increased monoamine levels in the synapse. Clinically, methylphenidate is prescribed for the symptomatic treatment of ADHD and narcolepsy; although lately, there has been an increased incidence of its use in individuals not meeting the criteria for these disorders. MPH has also been misused as a "cognitive enhancer" and as an alternative to other psychostimulants. Here, we investigate whether chronic or acute administration of MPH in mice at either 1 mg/kg or 10 mg/kg, affects cell number and gene expression in the basal ganglia. METHODOLOGY/PRINCIPAL FINDINGS: Through the use of stereological counting methods, we observed a significant reduction (∼20% in dopamine neuron numbers in the substantia nigra pars compacta (SNpc following chronic administration of 10 mg/kg MPH. This dosage of MPH also induced a significant increase in the number of activated microglia in the SNpc. Additionally, exposure to either 1 mg/kg or 10 mg/kg MPH increased the sensitivity of SNpc dopaminergic neurons to the parkinsonian agent 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP. Unbiased gene screening employing Affymetrix GeneChip® HT MG-430 PM revealed changes in 115 and 54 genes in the substantia nigra (SN of mice exposed to 1 mg/kg and 10 mg/kg MPH doses, respectively. Decreases in the mRNA levels of gdnf, dat1, vmat2, and th in the substantia nigra (SN were observed with both acute and chronic dosing of 10 mg/kg MPH. We also found an increase in mRNA levels of the pro-inflammatory genes il-6 and tnf-α in the striatum, although these were seen only at an acute dose of 10 mg/kg and not following chronic dosing. CONCLUSION: Collectively, our results suggest that chronic MPH usage in mice at doses spanning the therapeutic range in humans, especially at

  17. Treatment of beta amyloid 1–42 (Aβ1–42)-induced basal forebrain cholinergic damage by a non-classical estrogen signaling activator in vivo

    Science.gov (United States)

    Kwakowsky, Andrea; Potapov, Kyoko; Kim, SooHyun; Peppercorn, Katie; Tate, Warren P.; Ábrahám, István M.

    2016-01-01

    In Alzheimer’s disease (AD), there is a loss in cholinergic innervation targets of basal forebrain which has been implicated in substantial cognitive decline. Amyloid beta peptide (Aβ1–42) accumulates in AD that is highly toxic for basal forebrain cholinergic (BFC) neurons. Although the gonadal steroid estradiol is neuroprotective, the administration is associated with risk of off-target effects. Previous findings suggested that non-classical estradiol action on intracellular signaling pathways has ameliorative potential without estrogenic side effects. After Aβ1–42 injection into mouse basal forebrain, a single dose of 4-estren-3α, 17β-diol (estren), the non-classical estradiol pathway activator, restored loss of cholinergic cortical projections and also attenuated the Aβ1–42-induced learning deficits. Estren rapidly and directly phosphorylates c-AMP-response–element-binding-protein and extracellular-signal-regulated-kinase-1/2 in BFC neurons and restores the cholinergic fibers via estrogen receptor-α. These findings indicated that selective activation of non-classical intracellular estrogen signaling has a potential to treat the damage of cholinergic neurons in AD. PMID:26879842

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

    OpenAIRE

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

    2009-01-01

    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 electrophysiologic...

  19. A conserved TATA-less proximal promoter drives basal transcription from the urokinase-type plasminogen activator receptor gene

    DEFF Research Database (Denmark)

    Soravia, E; Grebe, A; De Luca, P

    1995-01-01

    The urokinase-type plasminogen activator receptor (uPAR) focuses at the cell surface the activation of pro-uPA and, hence, the formation of plasmin, thus enhancing directional extracellular proteolysis. To characterize the transcriptional regulatory mechanisms that control receptor expression, we...... have cloned an uPAR DNA segment containing upstream regulatory sequences from both the human and murine genomes. We report that a proximal promoter, contained within 180 bp from the major transcription start sites of the human uPAR gene, drives basal transcription. This region lacks TATA and CAAT boxes...

  20. cGMP activates a pH-sensitive leak K+ current in the presumed cholinergic neuron of basal forebrain.

    Science.gov (United States)

    Toyoda, Hiroki; Saito, Mitsuru; Sato, Hajime; Dempo, Yoshie; Ohashi, Atsuko; Hirai, Toshihiro; Maeda, Yoshinobu; Kaneko, Takeshi; Kang, Youngnam

    2008-05-01

    In an earlier study, we demonstrated that nitric oxide (NO) causes the long-lasting membrane hyperpolarization in the presumed basal forebrain cholinergic (BFC) neurons by cGMP-PKG-dependent activation of leak K+ currents in slice preparations. In the present study, we investigated the ionic mechanisms underlying the long-lasting membrane hyperpolarization with special interest in the pH sensitivity because 8-Br-cGMP-induced K+ current displayed Goldman-Hodgkin-Katz rectification characteristic of TWIK-related acid-sensitive K+ (TASK) channels. When examined with the ramp command pulse depolarizing from -130 to -40 mV, the presumed BFC neurons displayed a pH-sensitive leak K+ current that was larger in response to pH decrease from 8.3 to 7.3 than in response to pH decrease from 7.3 to 6.3. This K+ current was similar to TASK1 current in its pH sensitivity, whereas it was highly sensitive to Ba(2+), unlike TASK1 current. The 8-Br-cGMP-induced K+ currents in the presumed BFC neurons were almost completely inhibited by lowering external pH to 6.3 as well as by bath application of 100 microM Ba(2+), consistent with the nature of the leak K+ current expressed in the presumed BFC neurons. After 8-Br-cGMP application, the K+ current obtained by pH decrease from 7.3 to 6.3 was larger than that obtained by pH decrease from pH 8.3 to 7.3, contrary to the case seen in the control condition. These observations strongly suggest that 8-Br-cGMP activates a pH- and Ba(2+)-sensitive leak K+ current expressed in the presumed BFC neurons by modulating its pH sensitivity.

  1. A population level computational model of the basal ganglia that generates parkinsonian Local Field Potential activity.

    Science.gov (United States)

    Tsirogiannis, George L; Tagaris, George A; Sakas, Damianos; Nikita, Konstantina S

    2010-02-01

    Recordings from the basal ganglia's subthalamic nucleus are acquired via microelectrodes immediately prior to the application of Deep Brain Stimulation (DBS) treatment for Parkinson's Disease (PD) to assist in the selection of the final point for the implantation of the DBS electrode. The acquired recordings reveal a persistent characteristic beta band peak in the power spectral density function of the Local Field Potential (LFP) signals. This peak is considered to lie at the core of the causality-effect relationships of the parkinsonian pathophysiology. Based on LFPs acquired from human subjects during DBS for PD, we constructed a computational model of the basal ganglia on the population level that generates LFPs to identify the critical pathophysiological alterations that lead to the expression of the beta band peak. To this end, we used experimental data reporting that the strengths of the synaptic connections are modified under dopamine depletion. The hypothesis that the altered dopaminergic modulation may affect both the amplitude and the time course of the postsynaptic potentials is validated by the model. The results suggest a pivotal role of both of these parameters to the pathophysiology of PD.

  2. High basal melting forming a channel at the grounding line of Ross Ice Shelf, Antarctica

    Science.gov (United States)

    Marsh, Oliver J.; Fricker, Helen A.; Siegfried, Matthew R.; Christianson, Knut; Nicholls, Keith W.; Corr, Hugh F. J.; Catania, Ginny

    2016-01-01

    Antarctica's ice shelves are thinning at an increasing rate, affecting their buttressing ability. Channels in the ice shelf base unevenly distribute melting, and their evolution provides insight into changing subglacial and oceanic conditions. Here we used phase-sensitive radar measurements to estimate basal melt rates in a channel beneath the currently stable Ross Ice Shelf. Melt rates of 22.2 ± 0.2 m a-1 (>2500% the overall background rate) were observed 1.7 km seaward of Mercer/Whillans Ice Stream grounding line, close to where subglacial water discharge is expected. Laser altimetry shows a corresponding, steadily deepening surface channel. Two relict channels to the north suggest recent subglacial drainage reorganization beneath Whillans Ice Stream approximately coincident with the shutdown of Kamb Ice Stream. This rapid channel formation implies that shifts in subglacial hydrology may impact ice shelf stability.

  3. The high rate of prevalence of CT-detected basal ganglia calcification in neuropsychiatric (CNS) brucellosis.

    Science.gov (United States)

    Mousa, A M; Muhtaseb, S A; Reddy, R R; Senthilselvan, A; Al-Mudallal, D S; Marafie, A A

    1987-12-01

    Of 65 cases presenting with neuropsychiatric manifestations of brucellosis (CNS-brucellosis), 9(13.8%) had CT-detected basal ganglia calcification (BGC). Of these, 5 had meningitis and 4 had psychiatric manifestations as presenting features. The diagnosis of brucellosis was made by the finding of consistent history and physical findings and the presence of significantly elevated antibody titres and/or positive culture in the blood and/or CSF. In all the cases, BGC was in the form of punctate hyperdense non-enhancing shadows with average density 44.5-58.4 and maximum density 49-64HU. The calcification was unilateral in 3 cases, bilateral and symmetrical in 4 and bilateral but asymmetrical in 2. None of the cases had other predisposing conditions to BGC and in one of the cases did specific anti-brucella treatment effect a detectable change in the BGC. The finding of CT-detected BGC in patients coming from areas endemic for brucellosis should alert physicians to the possibility of underlying brucellar infection.

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

    Science.gov (United States)

    Rattan, Satish; Singh, Jagmohan; Kumar, Sumit; Phillips, Benjamin

    2015-06-01

    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.

  5. Genistein decreases basal hepatic cytochrome P450 1A1 protein expression and activity in Swiss Webster mice.

    Science.gov (United States)

    Froyen, Erik B; Steinberg, Francene M

    2016-05-01

    Soy consumption has been associated with risk reduction for chronic diseases such as cancer. One proposed mechanism for cancer prevention by soy is through decreasing cytochrome P450 1A1 (Cyp1a1) activity. However, it is not known with certainty which soy components modulate Cyp1a1, or the characteristics or mechanisms involved in the responses after short-term (<20 days) dietary treatment without concomitant carcinogen-mediated induction. Therefore, the objective was to test the hypothesis that physiologic concentrations of dietary genistein and/or daidzein will decrease basal hepatic Cyp1a1 protein expression and activity in male and female Swiss Webster mice via inhibiting the bindings of aryl hydrocarbon receptor (AhR)-AhR nuclear translocator (ARNT) and estrogen receptor-α to the Cyp1a1 promoter region xenobiotic response element. The mice were fed the AIN-93G diet supplemented with 1500 mg/kg of genistein or daidzein for up to 1 week. Genistein, but not daidzein, significantly decreased basal hepatic microsomal Cyp1a1 protein expression and activity. AhR protein expression was not altered. Molecular mechanisms were investigated in Hepa-1c1c7 cells treated with 5 μmol/L purified aglycones genistein, daidzein, or equol. Cells treated with genistein exhibited inhibitions in ARNT and estrogen receptor-α bindings to the Cyp1a1 promoter region. This study demonstrated that genistein consumption reduced constitutive hepatic Cyp1a1 protein expression and activity, thereby contributing to the understanding of how soy isoflavone aglycones modulate cytochrome P450 biotransformation enzymes.

  6. Basal hypothalamic pituitary adrenal axis activity and hippocampal volumes: the SMART-Medea study.

    Science.gov (United States)

    Knoops, Arnoud J G; Gerritsen, Lotte; van der Graaf, Yolanda; Mali, Willem P Th M; Geerlings, Mirjam I

    2010-06-15

    It has frequently been hypothesized that high levels of glucocorticoids have deleterious effects on the hippocampus and increase risk for cognitive decline and dementia, but no large-scale studies in humans have examined the direct relation between hippocampal volumes and hypothalamic-pituitary-adrenal axis activity. Cross-sectional analyses within the Second Manifestations of ARTerial disease-Magnetic Resonance (SMART)-Medea study, an ancillary study to the SMART-MR study on brain changes on magnetic resonance imaging (MRI) among patients with arterial disease. In 575 patients (mean age 62 +/- 9 years), diurnal cortisol rhythm was assessed with six saliva samples, collected at awakening; at 30, 45, and 60 min thereafter; and at 10 pm and 11 pm. A low dose of dexamethasone (.5 mg) was administered at 11 pm, and saliva was sampled the next morning at awakening. Volumetric measurements of the hippocampus were performed on a three-dimensional fast field echo T1-weighted scan with isotropic voxels. Mean total relative hippocampal volume was 6.0 +/- .7 mL. Linear regression analyses, adjusted for age, sex, vascular risk factors, and global brain atrophy showed that participants with higher evening levels and higher awakening levels after dexamethasone had smaller hippocampal volumes [B per SD (4.2) increase = -.09 mL; 95% confidence interval -.15 to -.03 mL and B per SD (2.5) increase = -.07 mL; 95% confidence interval -.13 to -.01 mL, respectively]. The awakening response was not significantly associated with hippocampal volumes. In this population, higher evening cortisol levels and reduced suppression after dexamethasone were associated with smaller hippocampal volumes, independent of total brain volume. The cortisol response after awakening was not associated with hippocampal volume.

  7. High-Density Genetic Map Construction and Gene Mapping of Basal Branching Habit and Flowers per Leaf Axil in Sesame

    Science.gov (United States)

    Mei, Hongxian; Liu, Yanyang; Du, Zhenwei; Wu, Ke; Cui, Chengqi; Jiang, Xiaolin; Zhang, Haiyang; Zheng, Yongzhan

    2017-01-01

    A good genetic map can provide the framework for quantitative trait loci (QTL) analysis, map-based gene cloning, and genome sequence assembling. The main objectives of this study were to develop a high-density genetic linkage map using specific length amplified fragment sequencing (SLAF-seq) in sesame. In the result, a high-resolution genetic map with 9,378 SLAF markers and 13 linkage groups (LGs) was constructed. The map spanned a total genetic distance of 1,974.23 cM, and the mean LG length was 151.86 cM, with an average genetic distance of 0.22 cM between adjacent markers. Based on the newly constructed genetic map, genes for basal branching habit (SiBH) and flowers per leaf axil (SiFA) were mapped to LG5 and LG11, respectively. PMID:28496450

  8. Sequence elements in the human osteocalcin gene confer basal activation and inducible response to hormonal vitamin D sub 3

    Energy Technology Data Exchange (ETDEWEB)

    Kerner, S.A.; Scott, R.A.; Pike, J.W. (Baylor College of Medicine, Houston, TX (USA))

    1989-06-01

    Osteoblast-specific expression of the bone protein osteocalcin is controlled at the transcriptional level by the steroid hormone 1{alpha},25-dihydroxyvitamin D{sub 3}. As this protein may represent a marker for bone activity in human disease, the authors examined the regulation of its expression at the molecular level by evaluating human osteocalcin gene promoter function. They describe regions within the promoter that contribute to basal expression of the gene in osteoblast-like cells in culture. Further, they define a 21-base-pair DNA element with the sequence 5{prime}-GTGACTCACCGGGTGAACGGG-3{prime}, which acts in cis to mediate 1{alpha},25-dihydroxyvitamin D{sub 3} inducibility of the osteocalcin gene. This response element bears sequence similarity with other short DNA segments, particularly those for estrogen and thyroid hormone, which act together with their respective trans-acting receptors to modulate gene transcription.

  9. Vismodegib in basal cell carcinoma.

    Science.gov (United States)

    Amaria, R N; Bowles, D W; Lewis, K D; Jimeno, A

    2012-07-01

    Vismodegib is a novel, small-molecule inhibitor of smoothened, a key component of the hedgehog signaling pathway. Increased hedgehog pathway signaling is critical in the development of hereditary and spontaneous basal cell carcinomas of the skin, and has been implicated in the development of a number of other tumors. In preclinical models, vismodegib demonstrated potent antitumor activity in hedgehog-dependent tumors, particularly basal cell carcinomas. Clinically, phase I and II studies showed dramatic anticancer activity in patients with advanced basal cell carcinomas. In January 2012, vismodegib was approved by the FDA for the treatment of unresectable or metastatic basal cell carcinomas of the skin.

  10. Contribution of KV7 Channels to Basal Coronary Flow and Active Response to Ischemia

    DEFF Research Database (Denmark)

    Khanamiri, Saereh; Soltysinska, Ewa; Jepps, Thomas A

    2013-01-01

    .5 activators produced relaxations, which were considerably less in arteries from hypertensive rats and were not mimicked by the KV7.1-specific activator R-L3. In isolated, perfused heart preparations, coronary flow rate increased in response to the KV7.2 to 7.5 activator (S)-1 and was diminished......The goal of the present study was to determine the role of KCNQ-encoded KV channels (KV7 channels) in the passive and active regulation of coronary flow in normotensive and hypertensive rats. In left anterior descending coronary arteries from normotensive rats, structurally different KV7.2 to 7....... Application of adenosine or A2A receptor agonist CGS-21680 produced concentration-dependent relaxations of coronary arteries from normotensive rats, which were attenuated by application of KV7 inhibitors. KV7 blockers also attenuated the ischemia-induced increase in coronary perfusion in Langendorff studies...

  11. Development of edge-activated liposomes for siRNA delivery to human basal epidermis for melanoma therapy.

    Science.gov (United States)

    Dorrani, Mania; Garbuzenko, Olga B; Minko, Tamara; Michniak-Kohn, Bozena

    2016-04-28

    Delivery of macromolecules such as siRNA into cells that reside in the basal epidermis of the skin is a major challenge due to the transport barriers that need to be overcome. siRNAs have potential therapeutic applications in various dermatological diseases such as psoriasis, atopic dermatitis, and cancer. Unfortunately, a low permeability of siRNA through the stratum corneum and epidermis has significantly limited its use for topical application. The objective of this study was to develop a topical siRNA delivery system that can permeate through the stratum corneum and viable epidermis and efficiently deposit therapeutic levels of siRNA to the basal epidermis/upper dermis where melanoma cells reside. To achieve this objective, a series of liposome compositions that contained various concentrations of edge activator in their structures were prepared and then complexed with siRNA at different ratios to generate a small library of liposome-siRNA complexes (lipoplexes) with different physicochemical properties. In this study we used melanoma as a disease model. Through use of quantitative imaging analysis, we identified the necessary design parameters for effective permeation of lipoplexes through the skin layers and deposition at the upper dermis. The ability of the formulated lipoplexes to internalize into melanoma cells, knockdown the expression of the BRAF protein and induce cell death in melanoma cells was studied by fluorescent microscopy, in-cell immunofluorescence assay and WST-1 cell proliferation assay. By providing direct quantitative and qualitative microscopy evidence, the results of this study demonstrate for the first time that the passive delivery of an edge-activated liposomal formulation can effectively carry siRNA through the stratum corneum and deposit it at the lower epidermis/upper dermis.

  12. Interactions of the alveolar macrophage and the fibroblast: regulation of basal and silica-activated eicosanoid production

    Energy Technology Data Exchange (ETDEWEB)

    Kuhn, D.C.; Demers, L.M. [Pennsylvania State University College of Medicine, Hershey, PA (United States). Dept. of Pathology

    1996-07-01

    Intercellular communication between lung cells has been shown to modulate physiology and pathophysiology in the lung. In particular, it is apparent that the alveolar macrophage (AM) and the fibroblast (Fb) interact via soluble signalling molecules to mediate inflation and fibrosis in response to a variety of noxious substances. To characterize the interaction of the AM and Fb in the relative production of proinflammatory eicosanoids in the lung, we evaluated basal and silica-activated production of prostaglandin E{sub 2} (PGE{sub 2}), thromboxane A{sub 2} (TXA{sub 2}) and leukotriene B{sub 4} (LTB{sub 4}) by human AM and Fb alone and when cultured together. Unstimulated AM and Fb cultured alone produced equal amounts of PGE{sub 2}. However, AM produced 20-fold more TXA{sub 2} and 3-fold more LTB{sub 4} than Fb. When Am and Fb were cultured together, either separated by a membrane or in physical contact with one another, the total production of TXA{sub 2} and LTB{sub 4} by both cell types was reduced by 70 to 90% while production of PGE{sub 2} was unaffected. When AM were first exposed to silica dust and then cocultured with Fb, the total production of PGE{sub 2} was decreased while that of TXA{sub 2} and LTB{sub 4} was unchanged compared to coculture in the absence of silica. The results of these studies suggest that basal eicosanoid synthesis may be modulated by the interaction of the AM and the Fb and that this communication is via soluble substances. In addition, dust-activated AM produce soluble mediators that may further alter lung eicosanoid production as part of a mechanism to modulate dust-induced pathophysiology. 20 refs., 3 figs.

  13. Aging-Related Correlation between Serum Sirtuin 1 Activities and Basal Metabolic Rate in Women, but not in Men

    Science.gov (United States)

    2017-01-01

    Sirtuin (SIRT) is a main regulator of metabolism and lifespan, and its importance has been implicated in the prevention against aging-related diseases. The purpose of this study was to identify the pattern of serum SIRT1 activity according to age and sex, and to investigate how serum SIRT1 activity is correlated with other metabolic parameters in Korean adults. The Biobank of Jeju National University Hospital, a member of the Korea Biobank Network, provided serum samples from 250 healthy adults. Aging- and metabolism-related factors were analyzed in serum, and the data were compared by the stratification of age and sex. Basal metabolic rate (BMR) decreased with age and was significantly lower in men in their fifties and older and in women in their forties and older compared with twenties in men and women, respectively. SIRT1 activities were altered by age and sex. Especially, women in their thirties showed the highest SIRT1 activities. Correlation analysis displayed that SIRT1 activity is positively correlated with serum triglyceride (TG) in men, and with waist circumference, systolic blood pressure, diastolic blood pressure, and serum TG in women. And, SIRT1 activity was negatively correlated with aspartate aminotransferase/alanine aminotransferase ratio in women (r = −0.183, p = 0.039). Positive correlation was observed between SIRT1 activity and BMR in women (r = 0.222, p = 0.027), but not in men. Taken together, these findings suggest the possibility that serum SIRT1 activities may be utilized as a biomarker of aging. In addition, positive correlation between SIRT1 activity and BMR in women suggests that serum SIRT1 activity may reflect energy expenditure well in human. PMID:28168178

  14. A review of pathologies associated with high T1W signal intensity in the basal ganglia on Magnetic Resonance Imaging

    OpenAIRE

    Zaitout, Zahia; Romanowski, Charles; Karunasaagarar, Kavitasagary; Connolly, Daniel; Batty, Ruth

    2014-01-01

    Summary With several functions and a fundamental influence over cognition and motor functions, the basal ganglia are the cohesive centre of the brain. There are several conditions which affect the basal ganglia and these have various clinical and radiological manifestations. Nevertheless, on magnetic resonance imaging there is a limited differential diagnosis for those conditions presenting with T1 weighted spin echo hyperintensity within the central nervous system in general and the basal ga...

  15. Npw38, a novel nuclear protein possessing a WW domain capable of activating basal transcription.

    Science.gov (United States)

    Komuro, A; Saeki, M; Kato, S

    1999-05-01

    We have found a novel cDNA encoding a 265 amino acid protein possessing a WW domain in our full-length cDNA bank. The WW domain was sandwiched between an acidic region and an acidic-basic amino acid repetitive region. In vitro transcription/translation of the cDNA produced a 38 kDa product that was also found in the cell lysate by western blot analysis. Thus this protein is named the nuclear protein containing a WW domain with a molecular mass of 38 kDa, Npw38. Immunofluorescence studies and expression of a fusion protein to a green fluorescent protein revealed that this protein is localized in the nucleus. Npw38 was shown to be capable of binding to a poly(rG) resin. Interestingly, the WW domain of Npw38 was found to function as a transcriptional activator in CHO cells using the GAL4 DNA-binding fusion system. Furthermore, the WW domains of human YAP and Pin1 were demonstrated to have a similar transcription-promoting activity. Combined mutation of the conserved first and second Trp residues and a hydrophobic triplet of TyrTyrTrp in the WW domain of Npw38 abolished the transcription-promoting activity, but single mutations of these sites did not. These results suggest that some WW domains potentially possess transcription-promoting activity in mammalian cells.

  16. Basal and exercise-induced neuroendocrine activation in patients with heart failure and in normal subjects

    DEFF Research Database (Denmark)

    Kjaer, Andreas; Appel, Jon; Hildebrandt, Per

    2004-01-01

    : Twenty-three newly-diagnosed CHF patients and 18 age- and gender-matched healthy subjects were exercised at two workloads, which were calculated to correspond to 50 and 75% of each individual's heart rate response. RESULTS: In CHF patients, baseline levels of ANP, BNP, AVP, PRA and ET-1 were elevated...... compared to healthy subjects. Exercise induced an increase in ANP, A and NA in both CHF patients and in normal subjects, however BNP was only increased in CHF patients and not in normal subjects. CONCLUSION: When CHF patients exercise at the same relative and submaximal level as age-matched healthy......BACKGROUND: Neuroendocrine activation is a pathophysiological response and an important prognostic marker in patients with chronic heart failure (CHF). Although chronic activation is well described, data on the responsiveness of the hormone systems are more limited. Most previous studies have...

  17. Adaptations in Basal and Hypothalamic–Pituitary–Adrenal-Activated Deoxycorticosterone Responses Following Ethanol Self-administration in Cynomolgus Monkeys

    Science.gov (United States)

    Jimenez, Vanessa A.; Porcu, Patrizia; Morrow, A. Leslie; Grant, Kathleen A.

    2017-01-01

    Acute ethanol activates the hypothalamic–pituitary–adrenal (HPA) axis, while long-term exposure results in a blunted neuroendocrine state, particularly with regards to the primary endpoint, cortisol, the primary glucocorticoid produced in the adrenal cortex. However, it is unknown if this dampened neuroendocrine status also influences other adrenocortical steroids. Plasma concentration of the mineralocorticoid and neuroactive steroid precursor deoxycorticosterone (DOC) is altered by pharmacological challenges of the HPA axis in cynomolgus monkeys. The present study investigated HPA axis regulation of circulating DOC concentration over the course of ethanol (4% w/v) induction and self-administration in non-human primates (Macaca fasciculata, n = 10). Plasma DOC, measured by radioimmunoassay, was compared at baseline (ethanol naïve), during schedule-induced polydipsia, and following 6-months of 22 h/day access to ethanol and water. The schedule induction of ethanol drinking did not alter basal DOC levels but selectively dampened the DOC response to pharmacological challenges aimed at the anterior pituitary (ovine corticotrophin-releasing hormone) and adrenal gland (post-dexamethasone adrenocorticotropin hormone), while pharmacological inhibition of central opioid receptors with naloxone greatly enhanced the DOC response during induction. Following 6 months of ethanol self-administration, basal DOC levels were increased more than twofold, while responses to each of the challenges normalized somewhat but remained significantly different than baseline. These data show that HPA axis modulation of the neuroactive steroid precursor DOC is markedly altered by the schedule induction of ethanol drinking and long-term voluntary ethanol self-administration. The consequences of chronic ethanol consumption on HPA axis regulation of DOC point toward allostatic modification of hypothalamic and adrenal function. PMID:28220108

  18. Basal lipolysis, not the degree of insulin resistance, differentiates large from small isolated adipocytes in high-fat fed mice.

    Science.gov (United States)

    Wueest, S; Rapold, R A; Rytka, J M; Schoenle, E J; Konrad, D

    2009-03-01

    Adipocytes in obesity are characterised by increased cell size and insulin resistance compared with adipocytes isolated from lean patients. However, it is not clear at present whether hypertrophy actually does drive adipocyte insulin resistance. Thus, the aim of the present study was to metabolically characterise small and large adipocytes isolated from epididymal fat pads of mice fed a high-fat diet (HFD). C57BL/6J mice were fed normal chow or HFD for 8 weeks. Adipocytes from epididymal fat pads were isolated by collagenase digestion and, in HFD-fed mice, separated into two fractions according to their size by filtration through a nylon mesh. Viability was assessed by lactate dehydrogenase and 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium assays. Basal and insulin-stimulated D-[U-(14)C]glucose incorporation and lipolysis were measured. Protein levels and mRNA expression were determined by western blot and real-time RT-PCR, respectively. Insulin-stimulated D-[U-(14)C]glucose incorporation into adipocytes isolated from HFD-fed mice was reduced by 50% compared with adipocytes from chow-fed mice. However, it was similar between small (average diameter 60.9 +/- 3.1 microm) and large (average diameter 83.0 +/- 6.6 microm) adipocytes. Similarly, insulin-stimulated phosphorylation of protein kinase B and AS160 were reduced to the same extent in small and large adipocytes isolated from HFD-mice. In addition, insulin failed to inhibit lipolysis in both adipocyte fractions, whereas it decreased lipolysis by 30% in adipocytes of chow-fed mice. In contrast, large and small adipocytes differed in basal lipolysis rate, which was twofold higher in the larger cells. The latter finding was associated with higher mRNA expression levels of Atgl (also known as Pnpla2) and Hsl (also known as Lipe) in larger adipocytes. Viability was not different between small and large adipocytes. Rate of basal lipolysis but not insulin responsiveness is different between small and large

  19. Mitogen-activated protein kinase signaling controls basal and oncostatin M-mediated JUNB gene expression.

    Science.gov (United States)

    Hicks, Mellissa J; Hu, Qiuping; Macrae, Erin; DeWille, James

    2015-05-01

    The mitogen-activated protein kinase (MAPK) pathway is aberrantly activated in many human cancers, including breast cancer. Activation of MAPK signaling is associated with the increased expression of a wide range of genes that promote cell survival, proliferation, and migration. This report investigated the influence of MAPK signaling on the regulation and expression of JUNB in human breast cancer cell lines. JUNB has been associated with tumor suppressor and oncogenic functions, with most reports describing JUNB as an oncogene in breast cancer. Our results indicated that JUNB expression is elevated in MCF10A(met), SKBR3, and MDA-MB-231 human breast cancer cell lines compared to nontransformed MCF10A mammary epithelial cells. Increased RAS/MAPK signaling in MCF10A(met) cells correlates with the increased association of RNA polymerase II (Pol II) phosphorylated on serine 5 (Pol IIser5p) with the JUNB proximal promoter. Pol IIser5p is the "transcription initiating" form of Pol II. Treatment with U0126, a MAPK pathway inhibitor, reduces Pol IIser5p association with the JUNB proximal promoter and reduces JUNB expression. Oncostatin M (OSM) enhances MAPK and STAT3 signaling and significantly induces JUNB expression. U0126 treatment reduces OSM-induced Pol IIser5p binding to the JUNB proximal promoter and JUNB expression, but does not reduce pSTAT3 levels or the association of pSTAT3 with the JUNB proximal promoter. These results demonstrate that the MAPK pathway plays a primary role in the control of JUNB gene expression by promoting the association of Pol IIser5p with the JUNB proximal promoter.

  20. 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.

  1. 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)H5]-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 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 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 NCT01986842. © 2017 American Society for Nutrition.

  2. Influence of acute exposure to high altitude on basal and postprandial plasma levels of gastroenteropancreatic peptides.

    Directory of Open Access Journals (Sweden)

    Rudolf L Riepl

    Full Text Available Acute mountain sickness (AMS is characterized by headache often accompanied by gastrointestinal complaints that vary from anorexia through nausea to vomiting. The aim of this study was to investigate the influence of high altitude on plasma levels of gastroenteropancreatic (GEP peptides and their association to AMS symptoms. Plasma levels of 6 GEP peptides were measured by radioimmunoassay in 11 subjects at 490 m (Munich, Germany and, after rapid passive ascent to 3454 m (Jungfraujoch, Switzerland, over the course of three days. In a second study (n = 5, the same peptides and ghrelin were measured in subjects who consumed standardized liquid meals at these two elevations. AMS symptoms and oxygen saturation were monitored. In the first study, both fasting (morning 8 a.m. and stimulated (evening 8 p.m. plasma levels of pancreatic polypeptide (PP and cholecystokinin (CCK were significantly lower at high altitude as compared to baseline, whereas gastrin and motilin concentrations were significantly increased. Fasting plasma neurotensin was significantly enhanced whereas stimulated levels were reduced. Both fasting and stimulated plasma motilin levels correlated with gastrointestinal symptom severity (r = 0.294, p = 0.05, and r = 0.41, p = 0.006, respectively. Mean O(2-saturation dropped from 96% to 88% at high altitude. In the second study, meal-stimulated integrated (= area under curve plasma CCK, PP, and neurotensin values were significantly suppressed at high altitude, whereas integrated levels of gastrin were increased and integrated VIP and ghrelin levels were unchanged. In summary, our data show that acute exposure to a hypobaric hypoxic environment causes significant changes in fasting and stimulated plasma levels of GEP peptides over consecutive days and after a standardized meal. The changes of peptide levels were not uniform. Based on the inhibition of PP and neurotensin release a reduction of the cholinergic tone can be postulated.

  3. High-frequency stimulation of the subthalamic nucleus selectively reverses dopamine denervation-induced cellular defects in the output structures of the basal ganglia in the rat.

    Science.gov (United States)

    Salin, Pascal; Manrique, Christine; Forni, Claude; Kerkerian-Le Goff, Lydia

    2002-06-15

    High-frequency stimulation (HFS) of the subthalamic nucleus (STN) is now recognized as an effective treatment for advanced Parkinson's disease, but the molecular basis of its effects remains unknown. This study examined the effects of unilateral STN HFS (2 hr of continuous stimulation) in intact and hemiparkinsonian awake rats on STN neuron metabolic activity and on neurotransmitter-related gene expression in the basal ganglia, by means of in situ hybridization histochemistry and immunocytochemistry. In both intact and hemiparkinsonian rats, this stimulation was found to induce c-fos protein expression but to decrease cytochrome oxidase subunit I mRNA levels in STN neurons. STN HFS did not affect the dopamine lesion-mediated overexpression of enkephalin mRNA or the decrease in substance P in the ipsilateral striatum. The lesion-induced increases in intraneuronal glutamate decarboxylase 67 kDa isoform (GAD67) mRNA levels on the lesion side were reversed by STN HFS in the substantia nigra, partially antagonized in the entopeduncular nucleus but unaffected in the globus pallidus. The stimulation did not affect neuropeptide or GAD67 mRNA levels in the side contralateral to the dopamine lesion or in intact animals. These data furnish the first evidence that STN HFS decreases the metabolic activity of STN neurons and antagonizes dopamine lesion-mediated cellular defects in the basal ganglia output structures. They provide molecular substrate to the therapeutic effects of this stimulation consistent with the current hypothesis that HFS blocks STN neuron activity. However, the differential impact of STN HFS on the effects of dopamine lesion among structures receiving direct STN inputs suggests that this stimulation may not cause simply interruption of STN outflow.

  4. Automatic basal slice detection for cardiac analysis

    Science.gov (United States)

    Paknezhad, Mahsa; Marchesseau, Stephanie; Brown, Michael S.

    2016-03-01

    Identification of the basal slice in cardiac imaging is a key step to measuring the ejection fraction (EF) of the left ventricle (LV). Despite research on cardiac segmentation, basal slice identification is routinely performed manually. Manual identification, however, has been shown to have high inter-observer variability, with a variation of the EF by up to 8%. Therefore, an automatic way of identifying the basal slice is still required. Prior published methods operate by automatically tracking the mitral valve points from the long-axis view of the LV. These approaches assumed that the basal slice is the first short-axis slice below the mitral valve. However, guidelines published in 2013 by the society for cardiovascular magnetic resonance indicate that the basal slice is the uppermost short-axis slice with more than 50% myocardium surrounding the blood cavity. Consequently, these existing methods are at times identifying the incorrect short-axis slice. Correct identification of the basal slice under these guidelines is challenging due to the poor image quality and blood movement during image acquisition. This paper proposes an automatic tool that focuses on the two-chamber slice to find the basal slice. To this end, an active shape model is trained to automatically segment the two-chamber view for 51 samples using the leave-one-out strategy. The basal slice was detected using temporal binary profiles created for each short-axis slice from the segmented two-chamber slice. From the 51 successfully tested samples, 92% and 84% of detection results were accurate at the end-systolic and the end-diastolic phases of the cardiac cycle, respectively.

  5. Effect of He-Ne laser irradiation on spontaneous contractive activity and basal tone level of rat portal vein

    Science.gov (United States)

    Petrishchev, Nikolai N.; Barabanova, Valeria V.; Mikhailova, Irina A.; Chephu, Svetlana G.

    2000-11-01

    To study the effect of He-Ne irradiation (632.8 nm, 15 mW/cm2) on spontaneous contractive activity the fragments of rat portal vein weremounted isometrically in Krebs buffer. Irradiation of vessel fragments by He-Ne laser during 3,5 and 10 min caused the decrease of ton up to 50%, which lasted in postirradiation period (the observation time - 10 min). The frequency of phasic and tonic contractions did not change, but the amplitude increased up to 40% as compared to the initial level. The decreased basal tone level and the increased amplitude of phasic oscillations lasted in postirradiation period. Adding NO synthasa blocator (N - nitro-L-arginine) to Krebs solution before irradiation caused no significant changes mentioned above parameters. Irradiation and coputing of the same parameters of spontaneous contractive activity of vena porta caused no effects, mentioned in the absence of the blocator. From the results it is concluded that the decrease of tone is evoked by the increase of EDRF production and cGMP. The increase of amplitude of phasic and tonic contractions is connected with increase of Ca++ entry in every contraction cycle as a result of membrane Ca++ pool increase.

  6. LGR5 expression is controled by IKKα in basal cell carcinoma through activating STAT3 signaling pathway

    Science.gov (United States)

    Xiao, Deshen; Lai, Weiwei; Pan, Yu; Jiang, Yiqun; Chen, Ling; Mao, Chao; Zhou, Jian; Xi, Sichuan; Cao, Ya; Liu, Shuang; Tao, Yongguang

    2016-01-01

    Basal cell carcinomas (BCC) of the skin are the most common of human cancers. The noncanonical NF-κB pathway is dependent on IKKα. However, the role of IKKα in BCC has not been elucidated. We show here that IKKα is expressed in the nucleus in BCC and non-malignant diseases. Nuclear IKKα could directly bind to the promoters of inflammation factors and LGR5, a stem cell marker, in turn, upregulating LGR5 expression through activation of STAT3 signaling pathway during cancer progression. Activation of STAT3 signaling pathway contributes LGR5 expression in dependent of IKKα after the interplay between STAT3 and IKKα. Meanwhile knockdown of IKKα inhibits tumor growth and transition of epithelial stage to mescheme stage. Taken together, we demonstrate that IKKα functions as a bone fide chromatin regulator in BCC, whose promoted expression contributes to oncogenic transformation via promoting expression stemness- and inflammatory- related genes. Our finding reveals a novel viewpoint for how IKKα may involve in BCCs tumor progression in the inflammatory microenvironment. PMID:27049829

  7. 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

    2017-01-01

    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% FiO2, 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. PMID:28255159

  8. Annexin A1 Preferentially Predicts Poor Prognosis of Basal-Like Breast Cancer Patients by Activating mTOR-S6 Signaling.

    Directory of Open Access Journals (Sweden)

    Anjana Bhardwaj

    Full Text Available Annexin A1 (ANXA1 is an anti-inflammatory protein reported to play a role in cell proliferation and apoptosis, and to be deregulated in breast cancer. The exact role of annexin A1 in the biology of breast cancer remains unclear. We hypothesized that the annexin A1 plays an oncogenic role in basal subtype of breast cancer by modulating key growth pathway(s.By mining the Cancer Genome Atlas (TCGA-Breast Cancer dataset and manipulating annexin A1 levels in breast cancer cell lines, we studied the role of annexin A1 in breast cancer and underlying signaling pathways.Our in-silico analysis of TCGA-breast cancer dataset demonstrated that annexin A1 mRNA expression is higher in basal subtype compared to luminal and HER2 subtypes. Within the basal subtype, patients show significantly poorer overall survival associated with higher expression of annexin A1. In both TCGA patient samples and cell lines, annexin A1 levels were significantly higher in basal-like breast cancer than luminal and Her2/neu-positive breast cancer. Stable annexin A1 knockdown in TNBC cell lines suppressed the mTOR-S6 pathway likely through activation of AMPK but had no impact on the MAPK, c-Met, and EGFR pathways. In a cell migration assay, annexin A1-depleted TNBC cells showed delayed migration as compared to wild-type cells, which could be responsible for poor patient prognosis in basal like breast cancers that are known to express higher annexin A1.Our data suggest that annexin A1 is prognostic only in patients with basal like breast cancer. This appears to be in part due to the role of annexin A1 in activating mTOR-pS6 pathway.

  9. High basal expression of interferon-stimulated genes in human bronchial epithelial (BEAS-2B cells contributes to influenza A virus resistance.

    Directory of Open Access Journals (Sweden)

    Lai-Giea Seng

    Full Text Available Respiratory epithelial cells play a key role in influenza A virus (IAV pathogenesis and host innate response. Transformed human respiratory cell lines are widely used in the study of IAV-host interactions due to their relative convenience, and inherent difficulties in working with primary cells. Transformed cells, however, may have altered susceptibility to virus infection. Proper characterization of different respiratory cell types in their responses to IAV infection is therefore needed to ensure that the cell line chosen will provide results that are of relevance in vivo. We compared replication kinetics of human H1N1 (A/USSR/77 IAVs in normal primary human bronchial epithelial (NHBE and two commonly used respiratory epithelial cell lines namely BEAS-2B and A549 cells. We found that IAV replication was distinctly poor in BEAS-2B cells in comparison with NHBE, A549 and Madin-Darby canine kidney (MDCK cells. IAV resistance in BEAS-2B cells was accompanied by an activated antiviral state with high basal expression of interferon (IFN regulatory factor-7 (IRF-7, stimulator of IFN genes (STING and IFN stimulated genes (ISGs. Treatment of BEAS-2B cells with a pan-Janus-activated-kinase (JAK inhibitor decreased IRF-7 and ISG expression and resulted in increased IAV replication. Therefore, the use of highly resistant BEAS-2B cells in IAV infection may not reflect the cytopathogenicity of IAV in human epithelial cells in vivo.

  10. Activation of MAPK pathways due to DUSP4 loss promotes cancer stem cell-like phenotypes in basal-like breast cancer.

    Science.gov (United States)

    Balko, Justin M; Schwarz, Luis J; Bhola, Neil E; Kurupi, Richard; Owens, Phillip; Miller, Todd W; Gómez, Henry; Cook, Rebecca S; Arteaga, Carlos L

    2013-10-15

    Basal-like breast cancer (BLBC) is an aggressive disease that lacks a clinically approved targeted therapy. Traditional chemotherapy is effective in BLBC, but it spares the cancer stem cell (CSC)-like population, which is likely to contribute to cancer recurrence after the initial treatment. Dual specificity phosphatase-4 (DUSP4) is a negative regulator of the mitogen-activated protein kinase (MAPK) pathway that is deficient in highly aggressive BLBCs treated with chemotherapy, leading to aberrant MAPK activation and resistance to taxane-induced apoptosis. Herein, we investigated how DUSP4 regulates the MAP-ERK kinase (MEK) and c-jun-NH2-kinase (JNK) pathways in modifying CSC-like behavior. DUSP4 loss increased mammosphere formation and the expression of the CSC-promoting cytokines interleukin (IL)-6 and IL-8. These effects were caused in part by loss of control of the MEK and JNK pathways and involved downstream activation of the ETS-1 and c-JUN transcription factors. Enforced expression of DUSP4 reduced the CD44(+)/CD24(-) population in multiple BLBC cell lines in a MEK-dependent manner, limiting tumor formation of claudin-low SUM159PT cells in mice. Our findings support the evaluation of MEK and JNK pathway inhibitors as therapeutic agents in BLBC to eliminate the CSC population.

  11. 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

    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...

  12. Common Features of Neural Activity during Singing and Sleep Periods in a Basal Ganglia Nucleus Critical for Vocal Learning in a Juvenile Songbird

    Science.gov (United States)

    Yanagihara, Shin; Hessler, Neal A.

    2011-01-01

    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. PMID:21991379

  13. 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.

  14. High discordance between punch biopsy and excision in establishing basal cell carcinoma subtype: analysis of 500 cases

    NARCIS (Netherlands)

    Wolberink, E.A.W.; Pasch, M.C.; Zeiler, M.; Erp, P.E.J. van; Gerritsen, M.J.P.

    2013-01-01

    Background Basal cell carcinoma (BCC) is the most frequently occurring cancer in humans. Worldwide incidences rise about 10% each year, increasing the burden on dermatologists, general practitioners and pathologists as well as increasing costs for the health care system. Increasingly non-surgical tr

  15. 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.

  16. 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.

    Science.gov (United States)

    Song, Xiulong; Wei, Zhengxi; Shaikh, Zahir A

    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 1-3μM 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.

  17. 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.

  18. Early L-dopa, but not pramipexole, restores basal ganglia activity in partially 6-OHDA-lesioned rats.

    Science.gov (United States)

    Marin, C; Bonastre, M; Mengod, G; Cortés, R; Giralt, A; Obeso, J A; Schapira, A H

    2014-04-01

    The most appropriate time for the initiation of dopaminergic symptomatic therapy in Parkinson's disease remains debatable. It has been suggested that early correction of basal ganglia pathophysiological abnormalities may have long-term beneficial effects. To test this hypothesis, we investigated the early and delayed actions of L-dopa and pramipexole, using a delayed-start protocol of treatment. The effects of early and delayed administration of these drugs on motor response, development of dyskinesias, neurogenesis and molecular markers in basal ganglia were studied in rats with a unilateral and partial 6-hydroxydopamine-induced nigrostriatal lesion. Ten days after lesioning, rats received treatment with: a) L-dopa methyl ester (25mg/kg with 6.25mg/kg of benserazide, i.p., twice a day); b) pramipexole (0.5mg/kg, sc, twice a day) or c) saline for 4weeks. Four weeks after treatment initiation, rats from the saline group were distributed in three groups that then received the following treatments: d) L-dopa, e) pramipexole or f) saline, for 4weeks more. Three animals in each treatment arm received 5-bromo-2-deoxyuridine injections (200mg/kg) 3days before starting treatment. When compared with delayed-start L-dopa, early-start L-dopa treatment induced a lower rotational response (ppramipexole, early-start pramipexole induced a higher rotational response (ppramipexole treatments. Our data support a possible restoration of basal ganglia physiological mechanisms by early-start L-dopa therapy.

  19. High-pressure study of the basal-plane anisotropy of the upper critical field of the topological superconductor SrxBi2Se3

    Science.gov (United States)

    Nikitin, A. M.; Pan, Y.; Huang, Y. K.; Naka, T.; de Visser, A.

    2016-10-01

    We report a high-pressure transport study of the upper-critical field Bc 2(T ) of the topological superconductor Sr0.15Bi2Se3 (Tc=3.0 K). Bc 2(T ) was measured for magnetic fields directed along two orthogonal directions, a and a*, in the trigonal basal plane. While superconductivity is rapidly suppressed at the critical pressure pc˜3.5 GPa, the pronounced two-fold basal-plane anisotropy Bc2 a/Bc2 a*=3.2 at T =0.3 K, recently reported at ambient pressure [Pan et al., Sci. Rep. 6, 28632 (2016), 10.1038/srep28632], is reinforced and attains a value of ˜5 at the highest pressure (2.2 GPa). The data reveal that the unconventional superconducting state with broken rotational symmetry is robust under pressure.

  20. Brain-derived neurotrophic factor enhances the basal rate of protein synthesis by increasing active eukaryotic elongation factor 2 levels and promoting translation elongation in cortical neurons.

    Science.gov (United States)

    Takei, Nobuyuki; Kawamura, Mihoko; Ishizuka, Yuta; Kakiya, Naomasa; Inamura, Naoko; Namba, Hisaaki; Nawa, Hiroyuki

    2009-09-25

    The constitutive and activity-dependent components of protein synthesis are both critical for neural function. Although the mechanisms controlling extracellularly induced protein synthesis are becoming clear, less is understood about the molecular networks that regulate the basal translation rate. Here we describe the effects of chronic treatment with various neurotrophic factors and cytokines on the basal rate of protein synthesis in primary cortical neurons. Among the examined factors, brain-derived neurotrophic factor (BDNF) showed the strongest effect. The rate of protein synthesis increased in the cortical tissues of BDNF transgenic mice, whereas it decreased in BDNF knock-out mice. BDNF specifically increased the level of the active, unphosphorylated form of eukaryotic elongation factor 2 (eEF2). The levels of active eEF2 increased and decreased in BDNF transgenic and BDNF knock-out mice, respectively. BDNF decreased kinase activity and increased phosphatase activity against eEF2 in vitro. Additionally, BDNF shortened the ribosomal transit time, an index of translation elongation. In agreement with these results, overexpression of eEF2 enhanced protein synthesis. Taken together, our results demonstrate that the increased level of active eEF2 induced by chronic BDNF stimulation enhances translational elongation processes and increases the total rate of protein synthesis in neurons.

  1. Excitatory synapses on dendritic shafts of the caudal basal amygdala exhibit elevated levels of GABAA receptor α4 subunits following the induction of activity-based anorexia.

    Science.gov (United States)

    Wable, Gauri S; Barbarich-Marsteller, Nicole C; Chowdhury, Tara G; Sabaliauskas, Nicole A; Farb, Claudia R; Aoki, Chiye

    2014-01-01

    Anorexia nervosa (AN) is an eating disorder characterized by self-imposed severe starvation, excessive exercise, and anxiety. The onset of AN is most often at puberty, suggesting that gonadal hormonal fluctuations may contribute to AN vulnerability. Activity-based anorexia (ABA) is an animal model that reproduces some of the behavioral phenotypes of AN, including the paradoxical increase in voluntary exercise following food restriction. The basal amygdala as well as the GABAergic system regulate trait anxiety. We therefore examined the subcellular distribution of GABA receptors (GABARs) in the basal amygdala of female pubertal rats and specifically of their α4 subunits, because expression of α4-containing GABARs is regulated by gonadal hormone fluctuations. Moreover, because these GABARs reduce neuronal excitability through shunting of EPSPs, we quantified the frequency of occurrence of these GABARs adjacent to excitatory synapses. Electron microscopic immunoctychemistry revealed no change in the frequency of association of α4 subunits with excitatory synapses on dendritic spines, whether in the anterior (Bregma -2.8 mm) or caudal (Bregma -3.8 mm) portion of the basal amygdala. Sholl analysis of golgi-stained neurons also revealed no change in the extent of dendritic branching by these densely spiny, pyramidal-like neurons. However, there was an increase of membranous α4 subunits near excitatory synapses on dendritic shafts, specifically in the caudal basal amygdala, and this was accompanied by a rise of α4 subunits intracellularly. Because most dendritic shafts exhibiting excitatory synapses are GABAergic interneurons, the results predict disinhibition, which would increase excitability of the amygdaloid network, in turn augmenting ABA animals' anxiety.

  2. Dimer-dependent intrinsic/basal activity of the class B G protein-coupled receptor PAC1 promotes cellular anti-apoptotic activity through Wnt/β-catenin pathways that are associated with dimer endocytosis.

    Directory of Open Access Journals (Sweden)

    Rongjie Yu

    Full Text Available The high expression of PACAP (pituitary adenylate cyclase-activating polypeptide-preferring receptor PAC1 is associated with nerve injury and tumors. Our previous report (Yu R, et al. PLoS One 2012; 7: e51811 confirmed the dimerization of PAC1 and found that the M-PAC1 mutation in the N-terminal first Cys/Ala lost the ability to form dimers. In this study, Chinese hamster ovary (CHO-K1 cells overexpressing wild-type PAC1 (PAC1-CHO had significantly higher anti-apoptotic activities against serum withdrawal-induced apoptosis associated with a lower caspase 3 activity and a higher Bcl-2 level in a ligand-independent manner than those of CHO cells overexpressing the mutant M-PAC1 (M-PAC1-CHO. PAC1-CHO had significantly higher β-catenin, cyclin D1 and c-myc levels corresponding to the Wnt/β-catenin signal than did M-PAC1-CHO. In addition, the Wnt/β-catenin pathway inhibitor XAV939 significantly inhibited the anti-apoptotic activities of PAC1-CHO. Top-flash assays demonstrated that PAC1-CHO had a significantly stronger Wnt/β-catenin signal than did M-PAC1-CHO. Acetylcysteine (NAC as an inhibitor of the dimerization of PAC1 inhibited the anti-apoptotic activities that were endowed by PAC1 and decreased the Wnt/β-catenin signal in Top-flash assays. In the PAC1 Tet (tetracycline-on inducible gene expression system by doxycycline (Dox, higher expression levels of PAC1 resulted in higher anti-apoptotic activities that were associated with a stronger Wnt/β-catenin signal. A similar correlation was also found with the down-regulation of PAC1 in the Neuro2a neuroblastoma cell. BiFC combined with fluorescence confocal imaging indicated that during serum-withdrawal-induced apoptosis, PAC1 dimers displayed significant endocytosis. These findings indicate that PAC1 has ligand-independent and dimer-dependent intrinsic/basal activity, conferring cells with anti-apoptotic activities against serum withdrawal, which is involved in the Wnt/β-catenin signal and

  3. 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 dietary inclusion of fiber at 10% from guar gum and cellulose and contributed by potatoes may adversely affect digestive use of dietary protein.

  4. Effect of phosphatidylserine on the basal and GABA-activated Cl- permeation across single nerve membranes from rabbit Deiters' neurons

    Energy Technology Data Exchange (ETDEWEB)

    Rapallino, M.V.; Cupello, A.; Mainardi, P.; Besio, G.; Loeb, C.W. (Centro di Studio per la Neurofisiologia Cerebrale, C.N.R., Genova (Italy))

    1990-06-01

    The permeation of labeled Cl- ions across single plasma membranes from Deiters' neurons has been studied in the presence of various concentrations of phosphatidylserine (PS) on their extracellular side. PS reduces significantly basal Cl- permeation only at 10(-5) M on the membrane exterior. No effect was found at other concentrations. GABA activable 36Cl- permeation is heavily reduced and almost abolished at 10(-11) - 10(-5) M phosphatidylserine. This exogenous phosphatidylserine effect is difficult to interpret in relation to the function of the endogenous phospholipid. However, it may be involved in the epileptogenic effect in vivo of exogenous phosphatidylserine administration to rats.

  5. Binding of a 100-kDa ubiquitous factor to the human prolactin promoter is required for its basal and hormone-regulated activity.

    Science.gov (United States)

    Peers, B; Nalda, A M; Monget, P; Voz, M L; Belayew, A; Martial, J A

    1992-11-15

    cAMP strongly stimulates the activity of the human prolactin (hPRL) promoter. We have previously shown that two types of cis-element are required for this cAMP regulation; binding sites for the pituitary-specific factor Pit-1, and the sequence spanning nucleotides -115 to -85 (named sequence A). Sequence A contains the TGACG motif found in the consensus sequence of the cAMP-responsive element (CRE). In this study, we show that a mutation in the TGACG motif of sequence A strongly reduces not only the cAMP regulation but also the Ca2+ regulation and basal activity of the hPRL promoter. Furthermore, gel-shift assays indicate that the mutation prevents binding of a ubiquitous factor which is not the CRE-binding protein. Southwestern experiments suggest that this ubiquitous factor's molecular mass is approximately 100 kDa. We conclude that binding of a 100-kDa ubiquitous factor to sequence A is required for full basal and hormonal regulation of hPRL-promoter activity.

  6. Occurrence of Highly Mature Organic Matter in Marine Black Shale Petroleum Source Rocks of Basal Cambrian from Northern Tarim Basin, China

    Institute of Scientific and Technical Information of China (English)

    YU Bingsong (于炳松); Hailiang DONG; CHEN Jianqiang (陈建强); CHEN Xiaolin (陈晓林); LIANG Shiyou (梁世友)

    2004-01-01

    More and more evidence indicates that organic matter (OM) in immature organic-rich sediments and sedimentary rocks is chemically adsorbed onto the outer surfaces of minerals and into interlayer (inner) surfaces of smectitic clay minerals in the form of amorphous molecular-scale carbon. But there have been few reports about the occurrence of highly mature OM in marine black shales (petroleum source rocks). The occurrence of highly mature OM in the black shales of basal Cambrian from northern Tarim Basin is studied in this paper. Based on the comprehensive analyses of total organic carbon contents (TOC), maximum thermolysis temperatures (T max ) of OM, mineral surface areas (MSA), and scanning electronic microscopic (SEM) and transmission electronic microscopic (TEM) observations of the black shales, it is concluded that the highly mature OM in the marine black shales of the basal Cambrian from northern Tarim Basin occurs in particulates ranging in size from 1 to 5 μm in diameter. Through the contrast of the occurrence of the highly mature OM in the black shales with that of the immature ones in modern marine continental margin sediments, some scientific problems are proposed, which are worth to study further in detail.

  7. Activating PIK3CA Mutations Induce an Epidermal Growth Factor Receptor (EGFR)/Extracellular Signal-regulated Kinase (ERK) Paracrine Signaling Axis in Basal-like Breast Cancer.

    Science.gov (United States)

    Young, Christian D; Zimmerman, Lisa J; Hoshino, Daisuke; Formisano, Luigi; Hanker, Ariella B; Gatza, Michael L; Morrison, Meghan M; Moore, Preston D; Whitwell, Corbin A; Dave, Bhuvanesh; Stricker, Thomas; Bhola, Neil E; Silva, Grace O; Patel, Premal; Brantley-Sieders, Dana M; Levin, Maren; Horiates, Marina; Palma, Norma A; Wang, Kai; Stephens, Philip J; Perou, Charles M; Weaver, Alissa M; O'Shaughnessy, Joyce A; Chang, Jenny C; Park, Ben Ho; Liebler, Daniel C; Cook, Rebecca S; Arteaga, Carlos L

    2015-07-01

    Mutations in PIK3CA, the gene encoding the p110α catalytic subunit of phosphoinositide 3-kinase (PI3K) have been shown to transform human mammary epithelial cells (MECs). These mutations are present in all breast cancer subtypes, including basal-like breast cancer (BLBC). Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), we identified 72 protein expression changes in human basal-like MECs with knock-in E545K or H1047R PIK3CA mutations versus isogenic MECs with wild-type PIK3CA. Several of these were secreted proteins, cell surface receptors or ECM interacting molecules and were required for growth of PIK3CA mutant cells as well as adjacent cells with wild-type PIK3CA. The proteins identified by MS were enriched among human BLBC cell lines and pointed to a PI3K-dependent amphiregulin/EGFR/ERK signaling axis that is activated in BLBC. Proteins induced by PIK3CA mutations correlated with EGFR signaling and reduced relapse-free survival in BLBC. Treatment with EGFR inhibitors reduced growth of PIK3CA mutant BLBC cell lines and murine mammary tumors driven by a PIK3CA mutant transgene, all together suggesting that PIK3CA mutations promote tumor growth in part by inducing protein changes that activate EGFR. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Activating PIK3CA Mutations Induce an Epidermal Growth Factor Receptor (EGFR)/Extracellular Signal-regulated Kinase (ERK) Paracrine Signaling Axis in Basal-like Breast Cancer*

    Science.gov (United States)

    Young, Christian D.; Zimmerman, Lisa J.; Hoshino, Daisuke; Formisano, Luigi; Hanker, Ariella B.; Gatza, Michael L.; Morrison, Meghan M.; Moore, Preston D.; Whitwell, Corbin A.; Dave, Bhuvanesh; Stricker, Thomas; Bhola, Neil E.; Silva, Grace O.; Patel, Premal; Brantley-Sieders, Dana M.; Levin, Maren; Horiates, Marina; Palma, Norma A.; Wang, Kai; Stephens, Philip J.; Perou, Charles M.; Weaver, Alissa M.; O'Shaughnessy, Joyce A.; Chang, Jenny C.; Park, Ben Ho; Liebler, Daniel C.; Cook, Rebecca S.; Arteaga, Carlos L.

    2015-01-01

    Mutations in PIK3CA, the gene encoding the p110α catalytic subunit of phosphoinositide 3-kinase (PI3K) have been shown to transform human mammary epithelial cells (MECs). These mutations are present in all breast cancer subtypes, including basal-like breast cancer (BLBC). Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), we identified 72 protein expression changes in human basal-like MECs with knock-in E545K or H1047R PIK3CA mutations versus isogenic MECs with wild-type PIK3CA. Several of these were secreted proteins, cell surface receptors or ECM interacting molecules and were required for growth of PIK3CA mutant cells as well as adjacent cells with wild-type PIK3CA. The proteins identified by MS were enriched among human BLBC cell lines and pointed to a PI3K-dependent amphiregulin/EGFR/ERK signaling axis that is activated in BLBC. Proteins induced by PIK3CA mutations correlated with EGFR signaling and reduced relapse-free survival in BLBC. Treatment with EGFR inhibitors reduced growth of PIK3CA mutant BLBC cell lines and murine mammary tumors driven by a PIK3CA mutant transgene, all together suggesting that PIK3CA mutations promote tumor growth in part by inducing protein changes that activate EGFR. PMID:25953087

  9. AKT1 Activation is Obligatory for Spontaneous BCC Tumor Growth in a Murine Model that Mimics Some Features of Basal Cell Nevus Syndrome.

    Science.gov (United States)

    Kim, Arianna L; Back, Jung Ho; Zhu, Yucui; Tang, Xiuwei; Yardley, Nathan P; Kim, Katherine J; Athar, Mohammad; Bickers, David R

    2016-10-01

    Patients with basal cell nevus syndrome (BCNS), also known as Gorlin syndrome, develop numerous basal cell carcinomas (BCC) due to germline mutations in the tumor suppressor PTCH1 and aberrant activation of Hedgehog (Hh) signaling. Therapies targeted at components of the Hh pathway, including the smoothened (SMO) inhibitor vismodegib, can ablate these tumors clinically, but tumors recur upon drug discontinuation. Using SKH1-Ptch1(+/-) as a model that closely mimics the spontaneous and accelerated growth pattern of BCCs in patients with BCNS, we show that AKT1, a serine/threonine protein kinase, is intrinsically activated in keratinocytes derived from the skin of newborn Ptch1(+/-) mice in the absence of carcinogenic stimuli. Introducing Akt1 haplodeficiency in Ptch1(+/-) mice (Akt1(+/-) Ptch1(+/-)) significantly abrogated BCC growth. Similarly, pharmacological inhibition of AKT with perifosine, an alkyl phospholipid AKT inhibitor, diminished the growth of spontaneous and UV-induced BCCs. Our data demonstrate an obligatory role for AKT1 in BCC growth, and targeting AKT may help reduce BCC tumor burden in BCNS patients. Cancer Prev Res; 9(10); 794-802. ©2016 AACR.

  10. Basal Tumor Cell Isolation and Patient-Derived Xenograft Engraftment Identify High-Risk Clinical Bladder Cancers

    Science.gov (United States)

    Skowron, K. B.; Pitroda, S. P.; Namm, J. P.; Balogun, O.; Beckett, M. A.; Zenner, M. L.; Fayanju, O.; Huang, X.; Fernandez, C.; Zheng, W.; Qiao, G.; Chin, R.; Kron, S. J.; Khodarev, N. N.; Posner, M. C.; Steinberg, G. D.; Weichselbaum, R. R.

    2016-01-01

    Strategies to identify tumors at highest risk for treatment failure are currently under investigation for patients with bladder cancer. We demonstrate that flow cytometric detection of poorly differentiated basal tumor cells (BTCs), as defined by the co-expression of CD90, CD44 and CD49f, directly from patients with early stage tumors (T1-T2 and N0) and patient-derived xenograft (PDX) engraftment in locally advanced tumors (T3-T4 or N+) predict poor prognosis in patients with bladder cancer. Comparative transcriptomic analysis of bladder tumor cells isolated from PDXs indicates unique patterns of gene expression during bladder tumor cell differentiation. We found cell division cycle 25C (CDC25C) overexpression in poorly differentiated BTCs and determined that CDC25C expression predicts adverse survival independent of standard clinical and pathologic features in bladder cancer patients. Taken together, our findings support the utility of BTCs and bladder cancer PDX models in the discovery of novel molecular targets and predictive biomarkers for personalizing oncology care for patients. PMID:27775025

  11. Proliferative activity of epidermal basal cells after wounding. AgNOR counts compared with bromodeoxyuridine reactivity in rats.

    Science.gov (United States)

    Rebolledo Godoy, A P; Rebolledo Godoy, M; Meissner, C; Oehmichen, M

    2001-04-01

    Quantitative changes in nucleolus organizer regions (NORs) are known markers of proliferation that can be demonstrated by a specific silver staining technique on paraffin-embedded sections. Wounding of skin induces proliferation of basal epidermal cells at the wound margin. The degree of proliferation depends on the survival time and can be measured by morphometric assessment of argyrophilic NORs (AgNORs). Following incision wounding of the pinnae, rats were allowed to survive for different intervals (7 rats per interval) up to 120 hours. Before each sacrifice, biopsies were taken and incubated in a bromodeoxyuridine (BrdU) solution, embedded in paraffin, and stained with an antibody against BrdU. At the same time morphometric analysis of AgNOR counts was performed on sections made from the same material. BrdU incorporating nuclei were assessed by simple counting, whereas morphometric analysis of AgNOR counts was computer aided. Both methods revealed an increase in the number of proliferating cells, a plateau phase being reached after about 36 hours, followed by a decline after about 70 hours. Both methods thus allowed a reliable temporal classification of the skin injury according to survival time. The molecular background of the AgNOR changes in relation to the proliferation of cellular elements is discussed in detail.

  12. Cognitive-Motor Interactions of the Basal Ganglia in Development

    Directory of Open Access Journals (Sweden)

    Gerry eLeisman

    2014-02-01

    Full Text Available Neural circuits linking activity in anatomically segregated populations of neurons in subcortical structures regulate complex behaviors such as walking, talking, language comprehension, and other cognitive functions associated with frontal lobes. The basal ganglia are also crucial elements in the circuits that confer human reasoning and adaptive function and are key elements in the control of reward-based learning, sequencing, discrete elements that constitute complete motor acts, and cognitive function. Imaging studies of intact humans and electrophysiologic studies of the brains and behavior of other species confirm these findings. We know that the relation between the basal ganglia and the cerebral cortical region allows for connections organized into discrete circuits. Rather than serving as a means for widespread cortical areas to gain access to the motor system, these loops reciprocally interconnect a large and diverse set of cerebral cortical areas with the basal ganglia. Neuronal activity within the basal ganglia associated with motor areas of the cerebral cortex is highly correlated with parameters of movement. Neuronal activity within the basal ganglia and cerebellar loops associated with the prefrontal cortex is related to the aspects of cognitive function. Thus, individual loops appear to be involved in distinct behavioral functions. Damage to the basal ganglia of circuits with motor areas of the cortex leads to motor symptoms, whereas damage to the subcortical components of circuits with non-motor areas of the cortex causes higher-order deficits. In this report, we review some of the anatomic, physiologic, and behavioral findings that have contributed to a reappraisal of function concerning the basal ganglia and cerebellar loops with the cerebral cortex and apply it in clinical applications to ADHD with biomechanics and a discussion of retention of primitive reflexes being highly associated with the condition.

  13. High basal defense gene expression determines sorghum resistance to the whorl-feeding insect southwestern corn borer.

    Science.gov (United States)

    Cheng, Wei-Ning; Lei, Jia-Xin; Rooney, William L; Liu, Tong-Xian; Zhu-Salzman, Keyan

    2013-06-01

    Southwestern corn borer (SWCB, Diatraea grandiosella) and fall armyworm (FAW, Spodoptera frugiperda) are major pests of sorghum in the southern United States. Host plant resistance is a desirable means for reducing plant damage and yield losses from both insects. In this study, we evaluated 12 sorghum lines for whorl-stage resistance to leaf-feeding SWCB and FAW in greenhouse and laboratory bioassays. Differential plant responses were detected against the two insects. Among 12 lines tested, CM1821, Della and PI196583 were resistant to both insects, while BTx2752 was largely susceptible. Line R.09110 was resistant to SWCB, but susceptible to FAW, whereas Redbine-60 was susceptible to SWCB, but not to FAW. In addition, we quantified various chemical components in the plants and determined their association with insect resistance. Tannin and chlorophyll in leaves did not show any significant correlation with resistance to either insects, but contents of soluble protein in general were negatively correlated with resistance to both insects. Endogenous soluble sugar and dhurrin were only positively correlated with resistance to SWCB, but not with FAW resistance. To gain some molecular insight into resistance mechanism of sorghum to SWCB, we performed qPCR reactions for key genes encoding enzymes involved in dhurrin and jasmonic acid (JA) biosynthesis on selected resistant or susceptible lines. Although these genes were rapidly and strongly induced by insect feeding in all lines, the observed resistance is likely explained by higher constitutive dhurrin contents in some resistant lines and higher basal JA biosynthesis in others. Our results suggest that sorghum utilizes multiple strategies to defend itself against SWCB.

  14. High basal defense gene expression determines sorghum resistance to the whorl-feeding insect southwestern corn borer

    Institute of Scientific and Technical Information of China (English)

    Wei-Ning Cheng; Jia-Xin Lei; William L.Rooney; Tong-Xian Liu; Keyan Zhu-Salzman

    2013-01-01

    Southwestern corn borer (SWCB,Diatraea grandiosella) and fall armyworm (FAW,Spodoptera frugiperda) are major pests of sorghum in the southern United States.Host plant resistance is a desirable means for reducing plant damage and yield losses from both insects.In this study,we evaluated 12 sorghum lines for whorl-stage resistance to leaf-feeding SWCB and FAW in greenhouse and laboratory bioassays.Differential plant responses were detected against the two insects.Among 12 lines tested,CM1821,Della and PI196583 were resistant to both insects,while BTx2752 was largely susceptible.Line R.09110 was resistant to SWCB,but susceptible to FAW,whereas Redbine-60 was susceptible to SWCB,but not to FAW.In addition,we quantified various chemical components in the plants and determined their association with insect resistance.Tannin and chlorophyll in leaves did not show any significant correlation with resistance to either insects,but contents of soluble protein in general were negatively correlated with resistance to both insects.Endogenous soluble sugar and dhurrin were only positively correlated with resistance to SWCB,but not with FAW resistance.To gain some molecular insight into resistance mechanism of sorghum to SWCB,we performed qPCR reactions for key genes encoding enzymes involved in dhurrin and jasmonic acid (JA) biosynthesis on selected resistant or susceptible lines.Although these genes were rapidly and strongly induced by insect feeding in all lines,the observed resistance is likely explained by higher constitutive dhurrin contents in some resistant lines and higher basal JA biosynthesis in others.Our results suggest that sorghum utilizes multiple strategies to defend itself against SWCB.

  15. 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.

  16. Wild-Type N-Ras, Overexpressed in Basal-like Breast Cancer, Promotes Tumor Formation by Inducing IL-8 Secretion via JAK2 Activation

    Directory of Open Access Journals (Sweden)

    Ze-Yi Zheng

    2015-07-01

    Full Text Available Basal-like breast cancers (BLBCs are aggressive, and their drivers are unclear. We have found that wild-type N-RAS is overexpressed in BLBCs but not in other breast cancer subtypes. Repressing N-RAS inhibits transformation and tumor growth, whereas overexpression enhances these processes even in preinvasive BLBC cells. We identified N-Ras-responsive genes, most of which encode chemokines; e.g., IL8. Expression levels of these chemokines and N-RAS in tumors correlate with outcome. N-Ras, but not K-Ras, induces IL-8 by binding and activating the cytoplasmic pool of JAK2; IL-8 then acts on both the cancer cells and stromal fibroblasts. Thus, BLBC progression is promoted by increasing activities of wild-type N-Ras, which mediates autocrine/paracrine signaling that can influence both cancer and stroma cells.

  17. Wild-Type N-Ras, Overexpressed in Basal-like Breast Cancer, Promotes Tumor Formation by Inducing IL-8 Secretion via JAK2 Activation.

    Science.gov (United States)

    Zheng, Ze-Yi; Tian, Lin; Bu, Wen; Fan, Cheng; Gao, Xia; Wang, Hai; Liao, Yi-Hua; Li, Yi; Lewis, Michael T; Edwards, Dean; Zwaka, Thomas P; Hilsenbeck, Susan G; Medina, Daniel; Perou, Charles M; Creighton, Chad J; Zhang, Xiang H-F; Chang, Eric C

    2015-07-21

    Basal-like breast cancers (BLBCs) are aggressive, and their drivers are unclear. We have found that wild-type N-RAS is overexpressed in BLBCs but not in other breast cancer subtypes. Repressing N-RAS inhibits transformation and tumor growth, whereas overexpression enhances these processes even in preinvasive BLBC cells. We identified N-Ras-responsive genes, most of which encode chemokines; e.g., IL8. Expression levels of these chemokines and N-RAS in tumors correlate with outcome. N-Ras, but not K-Ras, induces IL-8 by binding and activating the cytoplasmic pool of JAK2; IL-8 then acts on both the cancer cells and stromal fibroblasts. Thus, BLBC progression is promoted by increasing activities of wild-type N-Ras, which mediates autocrine/paracrine signaling that can influence both cancer and stroma cells.

  18. ΔNp63 promotes stem cell activity in mammary gland development and basal-like breast cancer by enhancing Fzd7 expression and Wnt signalling.

    Science.gov (United States)

    Chakrabarti, Rumela; Wei, Yong; Hwang, Julie; Hang, Xiang; Andres Blanco, Mario; Choudhury, Abrar; Tiede, Benjamin; Romano, Rose-Anne; DeCoste, Christina; Mercatali, Laura; Ibrahim, Toni; Amadori, Dino; Kannan, Nagarajan; Eaves, Connie J; Sinha, Satrajit; Kang, Yibin

    2014-10-01

    Emerging evidence suggests that cancer is populated and maintained by tumour-initiating cells (TICs) with stem-like properties similar to those of adult tissue stem cells. Despite recent advances, the molecular regulatory mechanisms that may be shared between normal and malignant stem cells remain poorly understood. Here we show that the ΔNp63 isoform of the Trp63 transcription factor promotes normal mammary stem cell (MaSC) activity by increasing the expression of the Wnt receptor Fzd7, thereby enhancing Wnt signalling. Importantly, Fzd7-dependent enhancement of Wnt signalling by ΔNp63 also governs tumour-initiating activity of the basal subtype of breast cancer. These findings establish ΔNp63 as a key regulator of stem cells in both normal and malignant mammary tissues and provide direct evidence that breast cancer TICs and normal MaSCs share common regulatory mechanisms.

  19. Basal Reinforced Piled Embankments

    NARCIS (Netherlands)

    Van Eekelen, S.J.M.

    2015-01-01

    A basal reinforced piled embankment consists of a reinforced embankment on a pile foundation. The reinforcement consists of one or more horizontal layers of geosynthetic reinforcement (GR) installed at the base of the embankment. The design of the GR is the subject of this thesis. A basal

  20. Basal Reinforced Piled Embankments

    NARCIS (Netherlands)

    Van Eekelen, S.J.M.

    2015-01-01

    A basal reinforced piled embankment consists of a reinforced embankment on a pile foundation. The reinforcement consists of one or more horizontal layers of geosynthetic reinforcement (GR) installed at the base of the embankment. The design of the GR is the subject of this thesis. A basal reinforce

  1. Basal Reinforced Piled Embankments

    NARCIS (Netherlands)

    Van Eekelen, S.J.M.

    2015-01-01

    A basal reinforced piled embankment consists of a reinforced embankment on a pile foundation. The reinforcement consists of one or more horizontal layers of geosynthetic reinforcement (GR) installed at the base of the embankment. The design of the GR is the subject of this thesis. A basal reinforce

  2. A Quantitative Model of the GIRK1/2 Channel Reveals That Its Basal and Evoked Activities Are Controlled by Unequal Stoichiometry of Gα and Gβγ

    Science.gov (United States)

    Rubinstein, Moran; Farhy-Tselnicker, Isabella; Styr, Boaz; Keren-Raifman, Tal; Dessauer, Carmen W.; Dascal, Nathan

    2015-01-01

    G protein-gated K+ channels (GIRK; Kir3), activated by Gβγ subunits derived from Gi/o proteins, regulate heartbeat and neuronal excitability and plasticity. Both neurotransmitter-evoked (Ievoked) and neurotransmitter-independent basal (Ibasal) GIRK activities are physiologically important, but mechanisms of Ibasal and its relation to Ievoked are unclear. We have previously shown for heterologously expressed neuronal GIRK1/2, and now show for native GIRK in hippocampal neurons, that Ibasal and Ievoked are interrelated: the extent of activation by neurotransmitter (activation index, Ra) is inversely related to Ibasal. To unveil the underlying mechanisms, we have developed a quantitative model of GIRK1/2 function. We characterized single-channel and macroscopic GIRK1/2 currents, and surface densities of GIRK1/2 and Gβγ expressed in Xenopus oocytes. Based on experimental results, we constructed a mathematical model of GIRK1/2 activity under steady-state conditions before and after activation by neurotransmitter. Our model accurately recapitulates Ibasal and Ievoked in Xenopus oocytes, HEK293 cells and hippocampal neurons; correctly predicts the dose-dependent activation of GIRK1/2 by coexpressed Gβγ and fully accounts for the inverse Ibasal-Ra correlation. Modeling indicates that, under all conditions and at different channel expression levels, between 3 and 4 Gβγ dimers are available for each GIRK1/2 channel. In contrast, available Gαi/o decreases from ~2 to less than one Gα per channel as GIRK1/2's density increases. The persistent Gβγ/channel (but not Gα/channel) ratio support a strong association of GIRK1/2 with Gβγ, consistent with recruitment to the cell surface of Gβγ, but not Gα, by GIRK1/2. Our analysis suggests a maximal stoichiometry of 4 Gβγ but only 2 Gαi/o per one GIRK1/2 channel. The unique, unequal association of GIRK1/2 with G protein subunits, and the cooperative nature of GIRK gating by Gβγ, underlie the complex pattern of

  3. Silymarin suppresses basal and stimulus-induced activation, exhaustion, differentiation, and inflammatory markers in primary human immune cells.

    Science.gov (United States)

    Lovelace, Erica S; Maurice, Nicholas J; Miller, Hannah W; Slichter, Chloe K; Harrington, Robert; Magaret, Amalia; Prlic, Martin; De Rosa, Stephen; Polyak, Stephen J

    2017-01-01

    Silymarin (SM), and its flavonolignan components, alter cellular metabolism and inhibit inflammatory status in human liver and T cell lines. In this study, we hypothesized that SM suppresses both acute and chronic immune activation (CIA), including in the context of HIV infection. SM treatment suppressed the expression of T cell activation and exhaustion markers on CD4+ and CD8+ T cells from chronically-infected, HIV-positive subjects. SM also showed a trend towards modifying CD4+ T cell memory subsets from HIV+ subjects. In the HIV-negative setting, SM treatment showed trends towards suppressing pro-inflammatory cytokines from non-activated and pathogen-associated molecular pattern (PAMP)-activated primary human monocytes, and non-activated and cytokine- and T cell receptor (TCR)-activated mucosal-associated invariant T (MAIT) cells. The data suggest that SM elicits broad anti-inflammatory and immunoregulatory activity in primary human immune cells. By using novel compounds to alter cellular inflammatory status, it may be possible to regulate inflammation in both non-disease and disease states.

  4. Telomerase activity in the regenerative basal layer of the epidermis inhuman skin and in immortal and carcinoma-derived skin keratinocytes.

    Science.gov (United States)

    Härle-Bachor, C; Boukamp, P

    1996-06-25

    Cellular senescence is defined by the limited proliferative capacity of normal cultured cells. Immortal cells overcome this regulation and proliferate indefinitively. One step in the immortalization process may be reactivation of telomerase activity, a ribonucleoprotein complex, which, by de novo synthesized telomeric TTAGGG repeats, can prevent shortening of the telomeres. Here we show that immortal human skin keratinocytes, irrespective of whether they were immortalized by simian virus 40, human papillomavirus 16, or spontaneously, as well as cell lines established from human skin squamous cell carcinomas exhibit telomerase activity. Unexpectedly, four of nine samples of intact human skin also were telomerase positive. By dissecting the skin we could show that the dermis and cultured dermal fibroblasts were telomerase negative. The epidermis and cultured skin keratinocytes, however, reproducibly exhibited enzyme activity. By separating different cell layers of the epidermis this telomerase activity could be assigned to the proliferative basal cells. Thus, in addition to hematopoietic cells, the epidermis, another example of a permanently regenerating human tissue, provides a further exception of the hypothesis that all normal human somatic tissues are telomerase deficient. Instead, these data suggest that in addition to contributing to the permanent proliferation capacity of immortal and tumor-derived keratinocytes, telomerase activity may also play a similar role in the lifetime regenerative capacity of normal epidermis in vivo.

  5. Structural basis for basal activity and autoactivation of abscisic acid (ABA) signaling SnRK2 kinases

    Energy Technology Data Exchange (ETDEWEB)

    Ng, Ley-Moy; Soon, Fen-Fen; Zhou, X. Edward; West, Graham M.; Kovach, Amanda; Suino-Powell, Kelly M.; Chalmers, Michael J.; Li, Jun; Yong, Eu-Leong; Zhu, Jian-Kang; Griffin, Patrick R.; Melcher, Karsten; Xu, H. Eric (Van Andel); (Scripps); (Purdue); (NU Singapore)

    2014-10-02

    Abscisic acid (ABA) is an essential hormone that controls plant growth, development, and responses to abiotic stresses. Central for ABA signaling is the ABA-mediated autoactivation of three monomeric Snf1-related kinases (SnRK2.2, -2.3, and -2.6). In the absence of ABA, SnRK2s are kept in an inactive state by forming physical complexes with type 2C protein phosphatases (PP2Cs). Upon relief of this inhibition, SnRK2 kinases can autoactivate through unknown mechanisms. Here, we report the crystal structures of full-length Arabidopsis thaliana SnRK2.3 and SnRK2.6 at 1.9- and 2.3-{angstrom} resolution, respectively. The structures, in combination with biochemical studies, reveal a two-step mechanism of intramolecular kinase activation that resembles the intermolecular activation of cyclin-dependent kinases. First, release of inhibition by PP2C allows the SnRK2s to become partially active because of an intramolecular stabilization of the catalytic domain by a conserved helix in the kinase regulatory domain. This stabilization enables SnRK2s to gain full activity by activation loop autophosphorylation. Autophosphorylation is more efficient in SnRK2.6, which has higher stability than SnRK2.3 and has well-structured activation loop phosphate acceptor sites that are positioned next to the catalytic site. Together, these data provide a structural framework that links ABA-mediated release of PP2C inhibition to activation of SnRK2 kinases.

  6. Brain MR imaging in patients with hepatic cirrhosis: relationship between high intensity signal in basal ganglia on T{sub 1}-weighted images and elemental concentrations in brain

    Energy Technology Data Exchange (ETDEWEB)

    Maeda, H. [Department of Radiology, Wakayama Medical College, 27-7, Wakayama City, 640 (Japan); Sato, M. [Department of Radiology, Wakayama Medical College, 27-7, Wakayama City, 640 (Japan); Yoshikawa, A. [Department of Radiology, Wakayama Medical College, 27-7, Wakayama City, 640 (Japan); Kimura, M. [Department of Radiology, Wakayama Medical College, 27-7, Wakayama City, 640 (Japan); Sonomura, T. [Department of Radiology, Wakayama Medical College, 27-7, Wakayama City, 640 (Japan); Terada, M. [Department of Radiology, Wakayama Medical College, 27-7, Wakayama City, 640 (Japan); Kishi, K. [Department of Radiology, Wakayama Medical College, 27-7, Wakayama City, 640 (Japan)

    1997-08-01

    In patients with hepatic cirrhosis, the globus pallidus and putamen show high intensity on T1-weighted MRI. While the causes of this high signal have been thought to include paramagnetic substances, especially manganese, no evidence for this has been presented. Autopsy in four cases of hepatic cirrhosis permitted measurement of metal concentrations in brain and histopathological examination. In three cases the globus pallidus showed high intensity on T1-weighted images. Mean manganese concentrations in globus pallidus, putamen and frontal white matter were 3.03 {+-} 0.38, 2.12 {+-} 0.37, and 1.38 {+-} 0.24 ({mu}g/g wet weight), respectively, being approximately four- to almost ten-fold the normal values. Copper concentrations in globus pallidus and putamen were also high, 50 % more than normal. Calcium, iron, zinc and magnesium concentrations were all normal. The fourth case showed no abnormal intensity in the basal ganglia and brain metal concentrations were all normal. Histopathologically, cases with showing high signal remarkable atrophy, necrosis, and deciduation of nerve cells and proliferation of glial cells and microglia in globus pallidus. These findings were similar to those in chronic manganese poisoning. On T1-weighted images, copper deposition shows no abnormal intensity. It is therefore inferred that deposition of highly concentrations of manganese may caused high signal on T1-weighted images and nerve cell death in the globus pallidus. (orig.). With 2 figs., 2 tabs.

  7. Identification of residues in the heme domain of soluble guanylyl cyclase that are important for basal and stimulated catalytic activity.

    Directory of Open Access Journals (Sweden)

    Padmamalini Baskaran

    Full Text Available Nitric oxide signals through activation of soluble guanylyl cyclase (sGC, a heme-containing heterodimer. NO binds to the heme domain located in the N-terminal part of the β subunit of sGC resulting in increased production of cGMP in the catalytic domain located at the C-terminal part of sGC. Little is known about the mechanism by which the NO signaling is propagated from the receptor domain (heme domain to the effector domain (catalytic domain, in particular events subsequent to the breakage of the bond between the heme iron and Histidine 105 (H105 of the β subunit. Our modeling of the heme-binding domain as well as previous homologous heme domain structures in different states point to two regions that could be critical for propagation of the NO activation signal. Structure-based mutational analysis of these regions revealed that residues T110 and R116 in the αF helix-β1 strand, and residues I41 and R40 in the αB-αC loop mediate propagation of activation between the heme domain and the catalytic domain. Biochemical analysis of these heme mutants allows refinement of the map of the residues that are critical for heme stability and propagation of the NO/YC-1 activation signal in sGC.

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

    OpenAIRE

    Fumika Mori; Ken-ichi Okada; Taishin Nomura; Yasushi Kobayashi

    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 ...

  9. Association of Notch pathway down-regulation with Triple Negative/Basal-like breast carcinomas and high tumor-infiltrating FOXP3+ Tregs.

    Science.gov (United States)

    Ortiz-Martínez, Fernando; Gutiérrez-Aviñó, Francisco José; Sanmartín, Elena; Pomares-Navarro, Eloy; Villalba-Riquelme, Cristina; García-Martínez, Araceli; Lerma, Enrique; Peiró, Gloria

    2016-06-01

    T regulatory cells (Tregs) are a lineage of lymphocytes involved in immune response suppression that are characterized by the expression of the forkhead box P3 (FOXP3) transcription factor. Notch pathway regulates FOXP3 transcription in Tregs, but its role in breast cancer is unknown. We aimed at studying whether Notch pathway regulates FOXP3 expression and Tregs content in breast cancer, and its association with luminal breast carcinomas. We analyzed by quantitative Real-Time PCR the mRNA levels of FOXP3, Notch pathway genes (Notch1, Notch2, Notch4 and Jagged1) and STAT3 in a series of 152 breast carcinomas including hormone receptor-positive and -negative phenotypes (luminal and Triple Negative/Basal-like). We also studied the protein expression of Notch1, STAT3 and FOXP3 by immunohistochemistry. High FOXP3 mRNA levels correlated with larger tumor size (p=0.010), histological grade 3 (p=0.008) and positive lymph-node status (p=0.031). Also, low levels of Notch pathway genes mRNA correlated with poor prognostic factors such as larger tumor size, positive lymph-node status, tumor phenotype and infiltrating tumor Tregs. A survival analysis for the patients showed that large tumor size, histological grade 3, vascular invasion, infiltrating Tregs and low Notch1 mRNA expression were significantly associated with a decreased patients' overall survival (p≤0.05). On a multivariate analysis, high Tregs content (HR=3.00, 95% CI 1.04-8.90, p=0.042) and low Notch1 mRNA levels (HR=3.33, 95% CI 1.02-10.86, p=0.046) were independent markers for overall survival. Our results support that the Notch pathway up-regulation promotes luminal breast carcinomas, whereas down-regulation correlates with the expression of FOXP3, favors tumor Tregs infiltration and associates with Triple Negative/Basal-like tumors.

  10. Model Predicts That MKP1 and TAB1 Regulate p38α Nuclear Pulse and Its Basal Activity through Positive and Negative Feedback Loops in Response to IL-1.

    Science.gov (United States)

    Singh, Raghvendra

    2016-01-01

    Interleukin-1 mediates inflammation and stress response through nuclear activity of p38α. Although IL-1 receptor is not degraded, p38α activation is transient. IL-1 also causes cell migration and EMT by modulating cell-cell junctions. Although molecules involved in p38 activation are known, mechanism of the transient nuclear response and its basal activity remains unknown. By mathematical modeling of IL1/p38 signaling network, we show that IL-1 induces robust p38α activation both in the nucleus and in the cytoplasm/membrane. While nuclear response consists of an acute phase, membrane response resembles a step change. Following stimulation, p38α activity returns to a basal level in absence of receptor degradation. While nuclear pulse is controlled by MKP1 through a negative feedback to pp38, its basal activity is controlled by both TAB1 and MKP1 through a positive feedback loop. Our model provides insight into the mechanism of p38α activation, reason for its transient nuclear response, and explanation of the basal activity of MKK3/6 and p38α, which has been experimentally observed by other groups.

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

    Science.gov (United States)

    Boone, Marc; Suppa, Mariano; Miyamoto, Makiko; Marneffe, Alice; Jemec, Gregor; Del Marmol, Veronique

    2016-06-01

    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 whereby an exponential function becomes linear has been implemented on HD-OCT signals. The relative attenuation factor (µraf ) at different skin layers could be assessed.. IV-OP of superficial BCC with high diagnostic accuracy (DA) and high negative predictive values (NPV) were (i) decreased µraf in lower part of epidermis and (ii) increased epidermal thickness (E-T). IV-OP of nodular BCC with good to high DA and NPV were (i) less negative µraf in papillary dermis compared to normal adjacent skin and (ii) significantly decreased E-T and papillary dermal thickness (PD-T). In infiltrative BCC (i) high µraf in reticular dermis compared to normal adjacent skin and (ii) presence of peaks and falls in reticular dermis had good DA and high NPV. HD-OCT seems to enable the combination of in vivo morphological analysis of cellular and 3-D micro-architectural structures with IV-OP analysis of BCC. This permits BCC sub-differentiation with higher accuracy than in vivo HD-OCT analysis of morphology alone.

  12. Spaced planar laminations formed by repetitive basal erosion and resurgence to high-sedimentation-rate regime: new insight from a bedform-like structures and laterally continuous exposures

    Science.gov (United States)

    Ishihara, Yoshiro; Yuri, Onishi; Tsuda, Keisuke; Yokokawa, Miwa

    2017-04-01

    Spaced planar laminations (SPL), or so-called traction carpet deposits, are frequently observed in deposits of sediment gravity flows. Several sedimentation models for a succession of inversely graded units have been suggested from field observations and flume experiments. The formation of the inversely graded unit could be summarized as follows: (1) abrupt sedimentation on freezing of an inversely graded layer, or (2) interruptions in flow causing a freezing of an inversely graded layer at the most basal part of flow. In either case, traction carpets as a bed load overlying the erosive boundary at the base of flow are required. Although some descriptions have reported SPLs forming antidune bedform-like structures and the association of SPLs with structureless massive deposits have not been clearly explained. In this study, we suggest a novel model of SPL formation by repetition of basal erosion and resurgence to high-sedimentation rates, based on detail examinations of SPLs both showing bedform-like structures and lateral extents of hundreds of meters. SPLs were investigated in the Mio-Pliocene Kiyosumi Formation in central Japan and the Miocene Aoshima Formation in southwest Japan. In a turbidite in the Kiyosumi Formation, SPLs show three mound-like structures, suggesting antidune bedforms with wavelengths of about 6 to 7 m. On the upcurrent flanks, SPLs show lenticular cross laminations or pinching out of units; those units do not show clear inverse grading. Rip-up mud clasts and relatively high-angle imbrications are also observed. On the other hand, SPLs on the downcurrent flanks show relatively clear inverse grading and transition downcurrent into a massive structureless bed. In the Aoshima Formation, SPLs with ca. 1 cm unit thickness continue approximately 50 m along a palaeocurrent direction without changes in thickness. These SPLs gradually transition upward into a massive structureless unit. From the observations described above, in addition to

  13. Loading and texture bias on the competitive slip activity for basal and prismatic slip systems in HCP alloys

    Science.gov (United States)

    Saxena, A. K.; Tewari, A.; Pant, P.

    2015-04-01

    Asymmetry in hexagonal crystal structure makes the occurrence of slip strongly dependent on the texture of sample. In titanium, which has a c/a ratio less than ideal, slip occurs preferentially on prismatic slip system. However other slip systems may get activated depending on the resolved shear stresses. In this paper we present results from plane strain compression experiments where the same area of the sample was imaged before and after deformation to document changes in microstructure. We then compare these results with a simple calculation of plastic strain based on activation of various slip systems depending on their respective critical resolved shear stresses. We show that incorporation of a strain rate dependent hardening parameter provides a reasonable match with the experimentally observed deformation behaviour of various grain orientations.

  14. Long-lasting memory deficits in mice withdrawn from cocaine are concomitant with neuroadaptations in hippocampal basal activity, GABAergic interneurons and adult neurogenesis.

    Science.gov (United States)

    Ladrón de Guevara-Miranda, David; Millón, Carmelo; Rosell-Valle, Cristina; Pérez-Fernández, Mercedes; Missiroli, Michele; Serrano, Antonia; Pavón, Francisco J; Rodríguez de Fonseca, Fernando; Martínez-Losa, Magdalena; Álvarez-Dolado, Manuel; Santín, Luis J; Castilla-Ortega, Estela

    2017-03-01

    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.

  15. 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

  16. 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

  17. Long-lasting memory deficits in mice withdrawn from cocaine are concomitant with neuroadaptations in hippocampal basal activity, GABAergic interneurons and adult neurogenesis

    Science.gov (United States)

    Ladrón de Guevara-Miranda, David; Millón, Carmelo; Rosell-Valle, Cristina; Pérez-Fernández, Mercedes; Missiroli, Michele; Serrano, Antonia; Pavón, Francisco J.; Rodríguez de Fonseca, Fernando; Martínez-Losa, Magdalena; Álvarez-Dolado, Manuel; Santín, Luis J.

    2017-01-01

    ABSTRACT 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. PMID:28138095

  18. 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.

  19. 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.

  20. Correlation of Glypican-4 Level with Basal Active Glucagon-Like Peptide 1 Level in Patients with Type 2 Diabetes Mellitus

    Science.gov (United States)

    Koh, Gwanpyo; Cho, Suk Ju; Yoo, So-Yeon; Chin, Sang Ouk

    2016-01-01

    Background Previous studies have reported that glypican-4 (GPC4) regulates insulin signaling by interacting with insulin receptor and through adipocyte differentiation. However, GPC4 has not been studied with regard to its effects on clinical factors in patients with type 2 diabetes mellitus (T2DM). We aimed to identify factors associated with GPC4 level in T2DM. Methods Between January 2010 and December 2013, we selected 152 subjects with T2DM and collected serum and plasma into tubes pretreated with aprotinin and dipeptidyl peptidase-4 inhibitor to preserve active gastric inhibitory polypeptide (GIP) and glucagon-like peptide 1 (GLP-1). GPC4, active GLP-1, active GIP, and other factors were measured in these plasma samples. We performed a linear regression analysis to identify factors associated with GPC4 level. Results The subjects had a mean age of 58.1 years, were mildly obese (mean body mass index [BMI], 26.1 kg/m2), had T2DM of long-duration (mean, 101.3 months), glycated hemoglobin 7.5%, low insulin secretion, and low insulin resistance (mean homeostatic model assessment of insulin resistance [HOMA-IR], 1.2). Their mean GPC4 was 2.0±0.2 ng/mL. In multivariate analysis, GPC4 was independently associated with age (β=0.224, P=0.009), and levels of active GLP-1 (β=0.171, P=0.049) and aspartate aminotransferase (AST; β=–0.176, P=0.043) after being adjusted for other clinical factors. Conclusion GPC4 was independently associated with age, active GLP-1, and AST in T2DM patients, but was not associated with HOMA-IR and BMI, which are well known factors related to GPC4. Further study is needed to identify the mechanisms of the association between GPC4 and basal active GLP-1 levels. PMID:27704740

  1. [Sodium in breads and snacks of high consumption in Costa Rica. Basal content and verification of nutrition labeling].

    Science.gov (United States)

    Montero-Campos, Maria de Los Ángeles; Blanco-Metzler, Adriana; Chan, Victoria Chan

    2015-03-01

    Bread is highly consumed by population, making it one of the main sources of sodium in the diet, despite being moderate in salt. Mean while, snacks have high sodium content, but are less consumed by the general population. The aim of this study was to determine by direct analysis the baseline of sodium in breads and snacks most consumed in Costa Rica and verify compliance with the Central American Technical Regulation on Nutritional Labeling. Foods samples were classified by type, trade mark, method and place of production. Samples were collected in supermarkets and bakeries in the Great Metropolitan Area between 2011 and 2012. Primary sample comprised 99 breads and 84 snacks, and analytical sample 33 and 28, respectively. The sodium content was determined by flame emission spectrophotometer. Breads showed between 496 and 744 mg/100 g sodium, 45% included nutritional labeling and 80% reported greater amount than found by direct analysis. Industrialized breads except the whole grain varieties, complied with regulations. In snacks, sodium content ranged from 276 to 1221 mg/100 g, all had nutritional labeling and 43% reported less content, in breach of the regulations. The study provides baseline data to initiate sodium reduction and direct analysis confirms that it is essential to know with certainty the sodium content in foods.

  2. High incidence and treatment of flexor carpi radialis tendinitis after trapeziectomy and abductor pollicis longus suspensionplasty for basal joint arthritis.

    Science.gov (United States)

    Low, T H; Hales, P F

    2014-10-01

    We reviewed the incidence and treatment of flexor carpi radialis tendinitis in 77 patients (81 thumbs) who had trapeziectomy and abductor pollicis longus suspensionplasty for thumb carpometacarpal joint arthritis. Eighteen patients, 20 wrists (25%) had flexor carpi radialis tendinitis. The onset was 2-10 months (mean 4.7) after surgery. Two cases had preceding trauma. Eight cases (40%) responded to splinting and steroid injection. Ten patients, 12 wrists (60%) underwent surgery after failing non-operative treatment. Eleven wrists had frayed or partially torn flexor carpi radialis tendon and one had a complete tendon rupture with pseudotendon formation. Flexor carpi radialis tenotomy and pseudotendon excision were performed. All operated patients obtained good pain relief initially post-operatively. However, the pain recurred in two patients after 8 months. One required a local steroid injection for localized tenderness at the site of the proximal tendon stump. The other patient required a revision operation for scaphotrapezoid impingement. Both obtained complete pain relief. Our study has shown a high incidence of flexor carpi radialis tendinitis following trapeziectomy and abductor pollicis longus suspensionplasty. Patients should be warned about this potential complication. © The Author(s) 2013.

  3. Culture of bovine ovarian follicle wall sections maintained the highly estrogenic profile under basal and chemically defined conditions

    Energy Technology Data Exchange (ETDEWEB)

    Vasconcelos, R.B. [Laboratório de Biotecnologia da Reprodução, Departamento de Ciências Fisiológicas, Instituto de Ciências Biológicas, Universidade de Brasília, Brasília, DF (Brazil); Salles, L.P. [Laboratório de Biologia Molecular, Departamento de Biologia Celular, Instituto de Ciências Biológicas, Universidade de Brasília, Brasília, DF (Brazil); Silva, I. Oliveira e; Gulart, L.V.M. [Laboratório de Biotecnologia da Reprodução, Departamento de Ciências Fisiológicas, Instituto de Ciências Biológicas, Universidade de Brasília, Brasília, DF (Brazil); Souza, D.K. [Laboratório de Biotecnologia da Reprodução, Departamento de Ciências Fisiológicas, Instituto de Ciências Biológicas, Universidade de Brasília, Brasília, DF (Brazil); Faculdade de Ceilândia, Universidade de Brasília, Ceilândia, DF (Brazil); Torres, F.A.G. [Laboratório de Biologia Molecular, Departamento de Biologia Celular, Instituto de Ciências Biológicas, Universidade de Brasília, Brasília, DF (Brazil); Bocca, A.L. [Departamento de Biologia Celular, Instituto de Ciências Biológicas, Universidade de Brasília, Brasília, DF (Brazil); Silva, A.A.M. Rosa e [Laboratório de Biotecnologia da Reprodução, Departamento de Ciências Fisiológicas, Instituto de Ciências Biológicas, Universidade de Brasília, Brasília, DF (Brazil)

    2013-08-16

    Follicle cultures reproduce in vitro the functional features observed in vivo. In a search for an ideal model, we cultured bovine antral follicle wall sections (FWS) in a serum-free defined medium (DM) known to induce 17β-estradiol (E{sub 2}) production, and in a nondefined medium (NDM) containing serum. Follicles were sectioned and cultured in NDM or DM for 24 or 48 h. Morphological features were determined by light microscopy. Gene expression of steroidogenic enzymes and follicle-stimulating hormone (FSH) receptor were determined by RT-PCR; progesterone (P{sub 4}) and E{sub 2} concentrations in the media were measured by radioimmunoassay. DM, but not NDM, maintained an FWS morphology in vitro that was similar to fresh tissue. DM also induced an increase in the expression of all steroidogenic enzymes, except FSH receptor, but NDM did not. In both DM and NDM, there was a gradual increase in P{sub 4} throughout the culture period; however, P{sub 4} concentration was significantly higher in NDM. In both media, E{sub 2} concentration was increased at 24 h, followed by a decrease at 48 h. The E{sub 2}:P{sub 4} ratio was higher in DM than in NDM. These results suggest that DM maintains morphological structure, upregulates the expression of steroidogenic enzyme genes, and maintains steroid production with a high E{sub 2}:P{sub 4} ratio in FWS cultures.

  4. The GIP receptor displays higher basal activity than the GLP-1 receptor but does not recruit GRK2 or arrestin3 effectively.

    Directory of Open Access Journals (Sweden)

    Suleiman Al-Sabah

    Full Text Available Glucagon-like peptide-1 (GLP-1 and glucose-dependent insulinotropic polypeptide (GIP are important regulators of insulin secretion, and their functional loss is an early characteristic of type 2 diabetes mellitus (T2DM. Pharmacological levels of GLP-1, but not GIP, can overcome this loss. GLP-1 and GIP exert their insulinotropic effects through their respective receptors expressed on pancreatic β-cells. Both the GLP-1 receptor (GLP-1R and the GIP receptor (GIPR are members of the secretin family of G protein-coupled receptors (GPCRs and couple positively to adenylate cyclase. We compared the signalling properties of these two receptors to gain further insight into why GLP-1, but not GIP, remains insulinotropic in T2DM patients.GLP-1R and GIPR were transiently expressed in HEK-293 cells, and basal and ligand-induced cAMP production were investigated using a cAMP-responsive luciferase reporter gene assay. Arrestin3 (Arr3 recruitment to the two receptors was investigated using enzyme fragment complementation, confocal microscopy and fluorescence resonance energy transfer (FRET.GIPR displayed significantly higher (P<0.05 ligand-independent activity than GLP-1R. Arr3 displayed a robust translocation to agonist-stimulated GLP-1R but not to GIPR. These observations were confirmed in FRET experiments, in which GLP-1 stimulated the recruitment of both GPCR kinase 2 (GRK2 and Arr3 to GLP-1R. These interactions were not reversed upon agonist washout. In contrast, GIP did not stimulate recruitment of either GRK2 or Arr3 to its receptor. Interestingly, arrestin remained at the plasma membrane even after prolonged (30 min stimulation with GLP-1. Although the GLP-1R/arrestin interaction could not be reversed by agonist washout, GLP-1R and arrestin did not co-internalise, suggesting that GLP-1R is a class A receptor with regard to arrestin binding.GIPR displays higher basal activity than GLP-1R but does not effectively recruit GRK2 or Arr3.

  5. Double-blind, randomized, multicentre, and active comparator controlled investigation of the effect of Pioglitazone, Metformin, and the combination of both on cardiovascular risk in patients with type 2 diabetes receiving stable basal insulin therapy: the PIOCOMB study

    Directory of Open Access Journals (Sweden)

    Kleine Iris

    2011-07-01

    Full Text Available Abstract Background We analyzed specific effects of an add-on therapy with pioglitazone compared to metformin and their combination in patients with basal insulin treatment on biomarkers of CV risk. Methods In this double-blind, randomized, multicentre, active comparator controlled trial, 121 patients with type 2 diabetes were enrolled. Inclusions: treatment with basal insulin, HbA1C 6.5% - 8.5%, age 30 - 75 years. After glargine therapy over 2 weeks for titration towards FBG ≤ 7.8 mmol/L, patients received either (A bid 850 mg metformin (n = 42, (B bid 15 mg pioglitazone (n = 40, or (C 30 mg pioglitazone plus 1.7 g metformin (n = 39 over 6 months. Matrix Metal Proteinase 9 (MMP-9 was primary objective, together with biomarkers of CV risk. Results Pioglitazone (B reduced MMP-9 versus baseline by 54.1 + 187.1 ng/mL, with metformin (A it was increased by 49.6 + 336.2 ng/mL (p = 0.0345; B vs. A, and with the combination of both (C it was decreased by 67.8 + 231.4 ng/mL (A vs. C: p = 0.0416; B vs. C: p = 0.8695. After logarithmic transformation due to high variances the exploratory results showed significance for A vs. B (p = 0.0043 and for A vs. C (p = 0.0289. Insulin dosage was reduced by 7.3 units in group B (p 1C was only significantly decreased in the combination group. No significant effects were observed for NFkB and PGFα. peripheral edema were seen in 11.9% vs. 40.0% vs. 20.5%, and weight change was -0.7 kg vs. +4.3 kg vs. +2.7 kg (A vs. B vs. C. Conclusions Addition of pioglitazone but not of metformin reduces MMP-9, hs-CRP and increased insulin sensitivity and adiponectin in this study. The combination of both had no additional effect on inflammation. Pioglitazone is suggested to be a rational add-on therapy to basal insulin in patients with high CV risk.

  6. Recombinant adeno-associated virus-mediated human kallikrein gene therapy prevents high-salt diet-induced hypertension without effect on basal blood pressure

    Institute of Scientific and Technical Information of China (English)

    Jiang-tao YAN; Tao WANG; Juan LI; Xiao XIAO; Dao-wen WANG

    2008-01-01

    Aim: To investigate the effects of the expression of human kallikrein (HK) on basal level blood pressure and high-salt diet-induced hypertension. Methods: We delivered the recombinant adeno-associated viral (rAAV)-mediated HK (rAAV-HK) gene and rAAV-LacZ (as the control) to normal, adult Sprague-Dawley rats. The animals were administered a normal diet in the first 4 weeks, followed by a high-salt diet. The expression of HK in the rats was assessed by ELISA and RT-PCR. Blood pressure and Na~ and K~ urinary excretion were monitored. Results: Under the normal diet, no obvious changes in blood pressure and Na+ and K+ urinary excretion were observed. When the high-salt diet was administered, sys-tolic blood pressure in the control animals receiving rAAV-LacZ increased from 122.3±1. 13 mmHg to a stable 142.4±1.77 mmHg 8 weeks after the high-salt diet. In contrast, there was no significant increase in the blood pressure in the rAAV-HK-treated group, in which the blood pressure remained at 121.9±1.73 mmHg. In the rAAV-HK-treated group, Na+ and K+ urinary excretion were higher compared to those of the control group. The morphological analysis showed that HK delivery remarkably protected against renal damage induced by a high-salt intake. Conclusion: Our study indicates that rAAV-mediated human tissue kallikrein gene delivery is a potentially safe method for the long-term treatment of hypertension. More importantly, it could be applied in the salt-sensitive population to prevent the occurrence of hypertension.

  7. Bed Conditions Inferred from Basal Earthquakes Beneath the Whillans Ice Plain, West Antarctica

    Science.gov (United States)

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

    2016-12-01

    Seismicity near the bed of fast-moving ice streams informs our understanding of basal controls on fast ice flow and the nature of small scale sources of basal resistance to sliding (sticky spots). Small basal earthquakes (BEQs) occurring at or near the base of ice streams express the current dominant basal stress state and allow observation of bed heterogeneities on spatial scales of 10s to 100s m that are difficult to observe otherwise. Temporal changes in the source mechanisms of these BEQs indicate changing basal conditions, and comparison of basal seismicity with GPS-determined ice velocity allows insight into the interplay between seismically active small basal sticky spots and fast ice motion. We present unique highly local observations of BEQs occurring beneath the Whillans Ice Plain, in West Antarctica, from a network of 13 surface and borehole seismometers overlying the WIP stick-slip cycle high tide initiation area. We record seismicity only 100s-1000s of m from basal seismic sources. We compare the occurrence of these BEQs with co-located GPS observations of ice surface velocity. We detect BEQs by cross correlation, using a catalog of hand-picked events with seismic wave arrivals at multiple sites. We then locate each BEQ and determine source parameters by fitting the S wave spectra: moment magnitude, stress drop, and rupture area. The basal earthquakes occur in families of remarkably repeatable events. The time interval between subsequent events within a BEQ family typically depends on ice velocity, but there is a complex interplay between ice velocity and source parameters. We also search for temporal changes in BEQ source parameters and seek to relate these changes to ice velocity measurements, thereby inferring changing bed conditions. Our preferred interpretation is that BEQs are rupture at or near the surface of an over-consolidated till package, suggesting that changes in basal seismicity may directly indicate changing subglacial till conditions.

  8. Integrated profiling of basal and luminal breast cancers.

    NARCIS (Netherlands)

    Adelaide, J.; Finetti, P.; Bekhouche, I.; Repellini, L.; Geneix, J.; Sircoulomb, F.; Charafe-Jauffret, E.; Cervera, N.; Desplans, J.; Parzy, D.; Schoenmakers, E.F.P.M.; Viens, P.; Jacquemier, J.; Birnbaum, D.; Bertucci, F.; Chaffanet, M.

    2007-01-01

    Basal and luminal are two molecular subtypes of breast cancer with opposite histoclinical features. We report a combined, high-resolution analysis of genome copy number and gene expression in primary basal and luminal breast cancers. First, we identified and compared genomic alterations in 45 basal

  9. 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.

  10. Metastatic Basal cell carcinoma accompanying gorlin syndrome.

    Science.gov (United States)

    Bilir, Yeliz; Gokce, Erkan; Ozturk, Banu; Deresoy, Faik Alev; Yuksekkaya, Ruken; Yaman, Emel

    2014-01-01

    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. High-Activity Dealloyed Catalysts

    Energy Technology Data Exchange (ETDEWEB)

    Kongkanand, Anusorn [General Motors LLC, Pontiac, MI (United States)

    2014-09-30

    Reduction of costly Pt usage in proton exchange membrane fuel cell electrodes is one of the major challenges towards development and commercialization of fuel cell vehicles. Although few have met the initial-kinetic activity requirements in a realistic fuel cell device, no catalyst material has ever met the demanding fuel cell durability targets set by DOE. In this project, a team of 4 universities and 2 companies came together to investigate a concept that appeared promising in preliminary non-fuel cell tests then to further develop the catalyst to a mature level ready for vehicle implementation. The team consists of academia with technical leadership in their respective areas, a catalyst supplier, and a fuel cell system integrator.The tightly collaborative project enabled development of a highly active and durable catalyst with performance that significantly exceeds that of previous catalysts and meets the DOE targets for the first time (Figure 1A). The catalyst was then further evaluated in full-active-area stack in a realistic vehicle operating condition (Figure 1B). This is the first public demonstration that one can realize the performance benefit and Pt cost reduction over a conventional pure Pt catalyst in a long-term realistic PEMFC system. Furthermore, systematic analyses of a range of catalysts with different performance after fuel cell testing allowed for correlation between catalyst microstructure and its electrocatalytic activity and durability. This will in turn aid future catalyst development.

  12. The mitochondrial genome and transcriptome of the basal dinoflagellate Hematodinium sp.: character evolution within the highly derived mitochondrial genomes of dinoflagellates.

    Science.gov (United States)

    Jackson, C J; Gornik, S G; Waller, R F

    2012-01-01

    The sister phyla dinoflagellates and apicomplexans inherited a drastically reduced mitochondrial genome (mitochondrial DNA, mtDNA) containing only three protein-coding (cob, cox1, and cox3) genes and two ribosomal RNA (rRNA) genes. In apicomplexans, single copies of these genes are encoded on the smallest known mtDNA chromosome (6 kb). In dinoflagellates, however, the genome has undergone further substantial modifications, including massive genome amplification and recombination resulting in multiple copies of each gene and gene fragments linked in numerous combinations. Furthermore, protein-encoding genes have lost standard stop codons, trans-splicing of messenger RNAs (mRNAs) is required to generate complete cox3 transcripts, and extensive RNA editing recodes most genes. From taxa investigated to date, it is unclear when many of these unusual dinoflagellate mtDNA characters evolved. To address this question, we investigated the mitochondrial genome and transcriptome character states of the deep branching dinoflagellate Hematodinium sp. Genomic data show that like later-branching dinoflagellates Hematodinium sp. also contains an inflated, heavily recombined genome of multicopy genes and gene fragments. Although stop codons are also lacking for cox1 and cob, cox3 still encodes a conventional stop codon. Extensive editing of mRNAs also occurs in Hematodinium sp. The mtDNA of basal dinoflagellate Hematodinium sp. indicates that much of the mtDNA modification in dinoflagellates occurred early in this lineage, including genome amplification and recombination, and decreased use of standard stop codons. Trans-splicing, on the other hand, occurred after Hematodinium sp. diverged. Only RNA editing presents a nonlinear pattern of evolution in dinoflagellates as this process occurs in Hematodinium sp. but is absent in some later-branching taxa indicating that this process was either lost in some lineages or developed more than once during the evolution of the highly unusual

  13. Neuropsychiatry of the basal ganglia

    OpenAIRE

    Ring, H.; Serra-Mestres, J

    2002-01-01

    This review aims to relate recent findings describing the role and neural connectivity of the basal ganglia to the clinical neuropsychiatry of basal ganglia movement disorders and to the role of basal ganglia disturbances in "psychiatric"' states. Articles relating to the relevant topics were initially collected through MEDLINE and papers relating to the clinical conditions discussed were also reviewed. The anatomy and connections of the basal ganglia indicate that these structures are import...

  14. BRCA1 dysfunction in sporadic basal-like breast cancer.

    Science.gov (United States)

    Turner, N C; Reis-Filho, J S; Russell, A M; Springall, R J; Ryder, K; Steele, D; Savage, K; Gillett, C E; Schmitt, F C; Ashworth, A; Tutt, A N

    2007-03-29

    Basal-like breast cancers form a distinct subtype of breast cancer characterized by the expression of markers expressed in normal basal/myoepithelial cells. Breast cancers arising in carriers of germline BRCA1 mutations are predominately of basal-like type, suggesting that BRCA1 dysfunction may play a role in the pathogenesis of sporadic basal-like cancers. We analysed 37 sporadic breast cancers expressing the basal marker cytokeratin 5/6, and age- and grade-matched controls, for downregulation of BRCA1. Although BRCA1 promoter methylation was no more common in basal-like cancers (basal 14% vs controls 11%, P=0.72), BRCA1 messenger RNA expression was twofold lower in basal-like breast cancers compared to matched controls (P=0.008). ID4, a negative regulator of BRCA1, was expressed at 9.1-fold higher levels in basal-like breast cancer (Prevealing heterogeneity in the basal-like phenotype. Finally, we found that 63% of metaplastic breast cancers, a rare type of basal-like cancers, had BRCA1 methylation, in comparison to 12% of controls (P<0.0001). The high prevalence of BRCA1 dysfunction identified in this study could be exploited in the development of novel approaches to targeted treatment of basal-like breast cancer.

  15. BRCA1-mutated and basal-like breast cancers have similar aCGH profiles and a high incidence of protein truncating TP53 mutations

    NARCIS (Netherlands)

    Holstege, H.; Horlings, H.M.; Velds, A.; Langerod, A.; Borresen-Dale, A.L.; van de Vijver, M.J.; Nederlof, P.M.; Jonkers, J.

    2010-01-01

    ABSTRACT: BACKGROUND: Basal-like breast cancers (BLBC) are aggressive breast cancers for which, so far, no targeted therapy is available because they typically lack expression of hormone receptors and HER2. Phenotypic features of BLBCs, such as clinical presentation and early age of onset, resemble

  16. 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.

  17. 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.

  18. 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.

  19. The basal ganglia and apraxia.

    Science.gov (United States)

    Pramstaller, P P; Marsden, C D

    1996-02-01

    caudate nucleus (three cases) rarely caused apraxia. The caudate lesions also had white matter involvement. Indeed, involvement of periventricular white matter alone caused apraxia. The vast majority of cases described with apraxia associated with deep lesions were in the left, dominant hemisphere. Ideomotor apraxia was described in most reports (72 out of 82 cases). Orofacial apraxia was less common (37 cases), usually with ideomotor apraxia. Ideational apraxia was rare (five cases), all with ideomotor apraxia. Apraxia was either bilateral or involved the left hand if there was a right hemiparesis, in those cases where descriptions were available. Lesions of the thalamus can sometimes cause apraxia (26 cases), even if there is no apparent involvement of white matter (12 cases). Small lesions confined to the thalamus can also sometimes cause apraxia (eight cases). The role of the thalamus in higher order motor control and apraxia remains to be determined. It is suggested that the term limb-kinetic apraxia should be retained to describe motor deficits in planning 'what to do', 'how to do it' and 'when to do it'; decisions which appear to involve activation of a complex distributed network of dorsolateral prefrontal cortex, supplementary motor areas, anterior cingulate regions and lateral premotor cortex. Such deficits need to be quantified. If they are present in patients with basal ganglia disease, over and above classical akinesia, bradykinesia and hypokinesia, then such patients could be said to exhibit limb-kinetic apraxia.

  20. 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.

  1. Glacier Basal Sliding in Two-Dimensions Quantified from Correlation of High-Resolution Satellite Imagery: A Case Study on Kennicott Glacier, Alaska

    Science.gov (United States)

    Armstrong, W. H., Jr.; Anderson, R. S.; Allen, J.; Rajaram, H.; Anderson, L. S.

    2014-12-01

    The coupling of glacial hydrology and sliding is a source of uncertainty for both ice flow modeling and prediction of future sea level rise. As basal sliding is required for a glacier to erode its bed, the spatial pattern of glacier sliding is also important for understanding alpine landscape evolution. We use multi-temporal WorldView satellite imagery (0.5 m pixel) to monitor the seasonal progression of glacier velocity across the terminal ~50 km2of Kennicott Glacier, Alaska. We employ the free image correlation software COSI-Corr to construct multiple velocity maps, using 2013 imagery with repeat times from 15 to 38 days. These short intervals between images allow us to analyze variations in glacier velocity over weekly to monthly timescales associated with hydrologically-induced basal sliding. By assuming that spring (March-April) glacier velocity results solely from viscous deformation, we produce spatially distributed maps of glacier sliding speed by differencing summer and spring ice surface speeds. For a given time, a large portion of our study reach slides with roughly uniform speed, despite significant variation in deformation speed. This suggests that glacier flow models in which basal sliding is taken simply to scale as ice surface velocity are unfounded. The upglacier end of our study reach slides at speeds that vary through the summer, whereas the terminal reach slides at a steady speed. The proportion of glacier motion due to sliding increases dramatically moving downglacier, making basal sliding especially important in the terminal region. Many formulations express glacier sliding as a function of effective pressure (ice pressure minus water pressure). If such formulations are correct, effective pressure varies little over large areas or is averaged over lengthscales equivalent to ~10 glacier thicknesses. Also, effective pressure is steady in the terminal region through the summer. We explore existing sliding laws to find which best describes the

  2. Somatotopic organization of the primate basal ganglia

    Directory of Open Access Journals (Sweden)

    Atsushi eNambu

    2011-04-01

    Full Text Available Somatotopic organization is a fundamental and key concept to understand how the cortico-basal ganglia loop works. It is also indispensable knowledge to perform stereotaxic surgery for movement disorders. Here I would like to describe the somatotopic organization of the basal ganglia, which consist of the striatum, subthalamic nucleus, globus pallidus and substantia nigra. Projections from motor cortical regions representing different body parts terminate in different regions of these nuclei. Basal ganglia neurons respond not only to the stimulation of the corresponding regions of the motor cortices, but also to active and passive movements of the corresponding body parts. On the basis of these anatomical and physiological findings, somatotopic organization can be identified in the motor territories of these nuclei in the basal ganglia. In addition, projections from functionally interrelated cortical areas partially converge through the cortico-basal ganglia loop, but nevertheless the somatotopy is still preserved. Disorganized somatotopy may explain, at least in part, the pathophysiology of movement disorders, such as Parkinson’s disease and dystonia.

  3. Vismodegib resistance in basal cell carcinoma: not a smooth fit.

    Science.gov (United States)

    Ridky, Todd W; Cotsarelis, George

    2015-03-09

    In this issue of Cancer Cell, two complementary papers by Atwood and colleagues and Sharpe and colleagues show that basal cell carcinomas resistant to the Smoothened (SMO) inhibitor vismodegib frequently harbor SMO mutations that limit drug binding, with mutations at some sites also increasing basal SMO activity.

  4. Detailed anatomy of the braincase of Macelognathus vagans Marsh, 1884 (Archosauria, Crocodylomorpha using high resolution tomography and new insights on basal crocodylomorph phylogeny

    Directory of Open Access Journals (Sweden)

    Juan Martin Leardi

    2017-01-01

    Full Text Available Background Macelognathus vagans Marsh, 1884 from the Late Jurassic Morrison Fm. of Wyoming was originally described as a dinosaur by Marsh and in 1971 Ostrom suggested crocodilian affinities. In 2005, Göhlich and collaborators identified new material of this species from Colorado as a basal crocodylomorph. However, a partial skull found in association with mandibular and postcranial remains was not described. Methods Due to the small size and delicate structures within the braincase, micro CT studies were performed on this specimen. The new anatomical information was incorporated in a phylogenetic dataset, expanding both character and taxon sampling. Results This new material reinforces the non-crocodyliform crocodylomorph affinities of Macelognathusas it bears a large otic aperture, unfused frontals and lacks ornamentation on the dorsal cranial bones. The internal structures also support these affinities as this specimen bears traits (i.e., heavily pneumatized and expanded basisphenoid; the presence of additional pneumatic features on the braincase; and the otoccipital-quadrate contact not present in most basal crocodylomorphs. Furthermore, the presence of a wide supraoccipital and a cranioquadrate passage are traits shared with Almadasuchus from the early Late Jurassic of Argentina. Macelognathus was recovered as one of the closest relatives of crocodyliforms, forming a clade (Hallopodidae with two other Late Jurassic taxa (Almadasuchus and Hallopus. Discussion The clade formed by Almadasuchus + Hallopus + Macelognathus, the Hallopodidae, is characterized by a higher degree of suturing of the braincase, posteriorly closed otic aperture (paralleled in mesoeucrocodylians and cursorial adaptations. Also, the phylogenetic position of this lineage of derived crocodylomorphs as the sister group of Crocodyliformes implies a large amount of unsampled record (ghost lineage, at least 50 million years.

  5. Detailed anatomy of the braincase of Macelognathus vagans Marsh, 1884 (Archosauria, Crocodylomorpha) using high resolution tomography and new insights on basal crocodylomorph phylogeny

    Science.gov (United States)

    Pol, Diego; Clark, James Matthew

    2017-01-01

    Background Macelognathus vagans Marsh, 1884 from the Late Jurassic Morrison Fm. of Wyoming was originally described as a dinosaur by Marsh and in 1971 Ostrom suggested crocodilian affinities. In 2005, Göhlich and collaborators identified new material of this species from Colorado as a basal crocodylomorph. However, a partial skull found in association with mandibular and postcranial remains was not described. Methods Due to the small size and delicate structures within the braincase, micro CT studies were performed on this specimen. The new anatomical information was incorporated in a phylogenetic dataset, expanding both character and taxon sampling. Results This new material reinforces the non-crocodyliform crocodylomorph affinities of Macelognathusas it bears a large otic aperture, unfused frontals and lacks ornamentation on the dorsal cranial bones. The internal structures also support these affinities as this specimen bears traits (i.e., heavily pneumatized and expanded basisphenoid; the presence of additional pneumatic features on the braincase; and the otoccipital-quadrate contact) not present in most basal crocodylomorphs. Furthermore, the presence of a wide supraoccipital and a cranioquadrate passage are traits shared with Almadasuchus from the early Late Jurassic of Argentina. Macelognathus was recovered as one of the closest relatives of crocodyliforms, forming a clade (Hallopodidae) with two other Late Jurassic taxa (Almadasuchus and Hallopus). Discussion The clade formed by Almadasuchus + Hallopus + Macelognathus, the Hallopodidae, is characterized by a higher degree of suturing of the braincase, posteriorly closed otic aperture (paralleled in mesoeucrocodylians) and cursorial adaptations. Also, the phylogenetic position of this lineage of derived crocodylomorphs as the sister group of Crocodyliformes implies a large amount of unsampled record (ghost lineage), at least 50 million years. PMID:28133565

  6. Do spotty high intensity regions found in basal ganglia on MRI T2-weighted brain images of elderly subjects indicate gliosis? Comparison of brain MRI T2-weighted images of elderly subjects and necropsy brain

    Energy Technology Data Exchange (ETDEWEB)

    Murai, Hiroshi; Hattori, Hideyuki; Matsumoto, Masayuki [Kanazawa Medical Univ., Uchinada, Ishikawa (Japan)

    2001-12-01

    Spotty high intensity regions are frequently found on the MRI T2-weighted brain images (T2WI) of elderly people. High intensity regions with a diameter of 3 mm or less have been considered as expanded perivascular space with no pathological implications on radiological diagnosis. However, its morphometrical basis is not clear. We examined the character of the spotty regions using brain MRI of brain screening subjects, and studied morphometrically arteriolosclerosis and perivascular tissue damage using necropsy brains of subjects aged 65 years and over. The size, number and location of the spotty high intensity regions were examined using the brain MRI of 109 T2WI which is used for brain screening at Kanazawa Medical University Hospital. The frontal lobe, temporal lobe, parietal lobe, hippocampus, midbrain and basal ganglia were sampled from 15 subjects aged 65 years and over, and the tissue sections were processed for HE stain, Elastica van Gieson stain and immunostaining with GFAP. We took photographs of brain arterioli and surrounding parenchyma with a digital telescope camera and the degree of arterioscleosis and tissue damage were assessed by measurements with an image analyzer. Spotty high intensity regions on T2WI with a diameter of 3 mm or less were observed in 95.5% subjects aged 65 years and over. 69.4% spotty region was observed in basal ganglia. There was a significant correlation between age and size. In morphometrical examination, at the basal ganglia, the density of GFAP-positive astrocytes in the perivascular tissue had a significant positive correlation with the proportional thickness of the adventitia, which is an index of arteriosclerosis, and a significant negative correlation with the size of the perivascular space. The results suggested that the spotty regions in the brain MRI of elderly people do not represent dilatations of the perivascular space, but is mild brain damage caused by arteriosclerosis. (author)

  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. Coupling in the cortico-basal ganglia circuit is aberrant in the ketamine model of schizophrenia.

    Science.gov (United States)

    Cordon, Ivan; Nicolás, María Jesús; Arrieta, Sandra; Lopetegui, Eneko; López-Azcárate, Jon; Alegre, Manuel; Artieda, Julio; Valencia, Miguel

    2015-08-01

    Recent studies have suggested the implication of the basal ganglia in the pathogenesis of schizophrenia. To investigate this hypothesis, here we have used the ketamine model of schizophrenia to determine the oscillatory abnormalities induced in the rat motor circuit of the basal ganglia. The activity of free moving rats was recorded in different structures of the cortico-basal ganglia circuit before and after an injection of a subanesthesic dose of ketamine (10mg/kg). Spectral estimates of the oscillatory activity, phase-amplitude cross-frequency coupling interactions (CFC) and imaginary event-related coherence together with animals׳ behavior were analyzed. Oscillatory patterns in the cortico-basal ganglia circuit were highly altered by the effect of ketamine. CFC between the phases of low-frequency activities (delta, 1-4; theta 4-8Hz) and the amplitude of high-gamma (~80Hz) and high-frequency oscillations (HFO) (~150Hz) increased dramatically and correlated with the movement increment shown by the animals. Between-structure analyses revealed that ketamine had also a massive effect in the low-frequency mediated synchronization of the HFO's across the whole circuit. Our findings suggest that ketamine administration results in an aberrant hypersynchronization of the whole cortico-basal circuit where the tandem theta/HFO seems to act as the main actor in the hyperlocomotion shown by the animals. Here we stress the importance of the basal ganglia circuitry in the ketamine model of schizophrenia and leave the door open to further investigations devoted to elucidate to what extent these abnormalities also reflect the prominent neurophysiological deficits observed in schizophrenic patients.

  9. Childhood onset generalised dystonia can be modelled by increased gain in the indirect basal ganglia pathway.

    Science.gov (United States)

    Sanger, T D

    2003-11-01

    Clinical experience suggests an important role of the indirect basal ganglia pathway in the genesis of childhood onset generalised dystonia, but it has been difficult to reconcile the increased muscle activity in dystonia with the current model of basal ganglia function in which the indirect pathway is considered primarily inhibitory. The aim of this study was to present a modification of the direct-indirect pathway model, in which the indirect pathway is inverting rather than purely inhibitory, so that while high signals are inhibited, low signals are amplified. As the basal ganglia may be a feedback loop that modifies cortical activity, instability from excessive gain in this feedback loop could explain features of dystonia. A detailed mathematical model is provided, together with simulations of cortical cell population spiking behaviour when connected through a basal ganglia loop. The simulations show that increased gain in the indirect pathway relative to the direct pathway can lead to unstable uncontrolled synchronous oscillations in cortex and basal ganglia. This behaviour could result in dystonia. The model provides a consistent explanation for the association of dystonia with parkinsonism and disorders characterised by dopamine depletion, the ability to treat some dystonias with dopamine, the ability of neuroleptic drug treatment to cause an acute dystonic reaction treatable with anticholinergic drugs, and the ability of pallidotomy or deep brain stimulation of the internal pallidum to alleviate symptoms of generalised dystonia.

  10. High-intensity interval training without weight loss improves exercise but not basal or insulin-induced metabolism in overweight/obese African American women.

    Science.gov (United States)

    Arad, Avigdor D; DiMenna, Fred J; Thomas, Naketa; Tamis-Holland, Jacqueline; Weil, Richard; Geliebter, Allan; Albu, Jeanine B

    2015-08-15

    The purpose of this randomized controlled clinical trial was to determine the effect of a 14-week high-intensity interval training (HIIT) intervention with weight stability on metabolic flexibility, insulin sensitivity, and cardiorespiratory fitness in sedentary, premenopausal, nondiabetic, overweight/obese African American women. Twenty-eight subjects were allocated to one of two groups: HIIT, which performed three sessions per week of four high-intensity cycling intervals, or a control group (CON), which maintained their normal level of physical activity. Diet was controlled for all subjects to ensure weight stability. Pre- and postintervention (pre/post), subjects completed an incremental cycling test to limit of tolerance and, following a 10-day high-fat controlled feeding period, a euglycemic-hyperinsulinemic clamp to determine insulin sensitivity and substrate oxidation. Nine members of HIIT (age, 29 ± 4 yr; body mass, 90.1 ± 13.8 kg) and eleven members of CON (age, 30 ± 7 yr; body mass, 85.5 ± 10.7 kg) completed the study. HIIT experienced an increased limit of tolerance (post, 1,124 ± 202 s; pre, 987 ± 146 s; P exchange threshold (post, 1.29 ± 0.34 liters/min; pre, 0.97 ± 0.23 liters/min; P rate compared with CON (P flexibility were not different in HIIT compared with CON. High-intensity interval training with weight stability increased exercise fat oxidation and tolerance in subjects at risk for diabetic progression, but did not improve insulin sensitivity or fat oxidation in the postabsorptive or insulin-stimulated state.

  11. Choosing the Right Basal Reader.

    Science.gov (United States)

    Robbins, Ruth H.

    1980-01-01

    Looks at factors in the textbook publishing industry, especially costs and censorship, which affect the quality of available reading series. Notes the problem of readability and content bias. Finally, presents a checklist of basal reader evaluation criteria. (SJL)

  12. Reduced basal and novelty-induced levels of activity-regulated cytoskeleton associated protein (Arc) and c-Fos mRNA in the cerebral cortex and hippocampus of APPswe/PS1ΔE9 transgenic mice

    DEFF Research Database (Denmark)

    Christensen, Ditte Z; Thomsen, Morten Skøtt; Mikkelsen, Jens D

    2013-01-01

    Activity-regulated cytoskeletal-associated protein (Arc) and c-Fos are immediate early gene (IEG) products induced by novelty in the hippocampus and involved in the consolidation of synaptic plasticity and long-term memory. We investigated whether induction of arc and c-fos after exposure...... to a novel open field environment was compromised in different neocortical areas and the hippocampal formation in APP/PS1ΔE9 transgenic mice characterized by pronounced accumulation and deposition of beta amyloid (Aβ). Notably, the basal level of Arc and c-fos mRNA in the neocortex was significantly lower...... in APP/PS1ΔE9 as in the wild-type mice. In contrast, synaptophysin levels did not differ between mutant and wild type mice, suggesting that the observed effect was not due to a general decrease in the number of presynapses. These data suggest a reduction in basal and novelty-induced neuronal activity...

  13. Elevada frecuencia de dislipidemia y glucemia basal alterada en una población Peruana de altura High frequency of dyslipidemia and impaired fasting glycemia in a high altitude Peruvian population

    Directory of Open Access Journals (Sweden)

    Germán Málaga

    2010-12-01

    Full Text Available Se realizó un estudio transversal en la comunidad altoandina de Lari (3600 msnm en Arequipa, Perú. Se evaluó el índice de masa corporal (IMC, niveles de glucosa y perfil de lípidos en 74 pobladores mayores de 18 años. La edad promedio fue de 51,7 ± 18,0 años, 62,2% fueron mujeres, el IMC promedio fue de 25,6 ± 3,7. Se encontró una prevalencia de hipercolesterolemia de 40,6%, "HDL anormalmente bajo" en 77% de la población (93,5% en mujeres frente a 50% en varones; p126 mg/dL de 1,3%. En conclusión, esta población altoandina tiene niveles elevados de glucemia basal alterada en ayunas, hipercolesterolemia y HDL anormalmente bajo. Se deben tomar en cuenta estos hallazgos para realizar intervenciones en poblaciones de altura para evitar futuras complicaciones cardiovasculares.We performed a cross sectional study in Lari (3600 m, a highland rural community from Arequipa, Peru. We evaluated a body mass index (BMI, glycemia and lipid profile in 74 over 18 year persons. The mean age was 51.7 ± 18.0 years, 62.2% were women, mean of BMI was 25.6 ± 3.7. Prevalence of hypercholesterolemia was 40.6%, "low HDL" in 77% of the population (93.5% in women vs 50% in men, p <0.001 and elevated level of LDL was 71.7%. The prevalence of impaired fasting glycemia was 27%. In conclusion, we found high prevalence of impaired fasting glycemia, hypercholesterolemia and especially "low HDL" in high altitude rural natives. These findings must be considered to realize interventions in high altitude populations to avoid future cardiovascular complications.

  14. Basal cell carcinoma is associated with high TNF-alpha release but nor with TNF-alpha polymorphism at position--308

    DEFF Research Database (Denmark)

    Skov, Lone; Allen, Michael H; Bang, Bo

    2003-01-01

    The mechanisms underlying induction of UVB-induced immunosuppression are not fully understood, but tumor necrosis factor alpha (TNF-alpha) is suggested to play a central role. A single base pair polymorphism at position --308 in the promoter region of the TNF-alpha gene associated with an enhance...... with increased TNF-alpha production and BCC and necessary.......The mechanisms underlying induction of UVB-induced immunosuppression are not fully understood, but tumor necrosis factor alpha (TNF-alpha) is suggested to play a central role. A single base pair polymorphism at position --308 in the promoter region of the TNF-alpha gene associated with an enhanced...... secretion of TNF-alpha has been identified in humans. We have therefore investigated the association of the --308 polymorphism with the risk of basal cell carcinoma (BCC) in humans. The frequency of TNF G and TNF A alleles among Caucasian patients with a previous BCC (n=191) and health adults (n-107) were...

  15. High-resolution foraminiferal biostratigraphy of Upper Maastrichtian to basal Danian strata, Danish Central Graben. M-10X (Dan Field), E-5X (Tyra SE Field)

    Energy Technology Data Exchange (ETDEWEB)

    Lassen, S.; Rasmussen, J.A.

    2004-07-01

    Benthic and planktic foraminiferids from the Upper Maastrichtian to Lower Danian part of the wells M-10X and E-5X were thoroughly analysed with the aim to establish a detailed biostratigraphic framework for the southern part of the Danish Central Graben area. The Upper Maastrichtian sediments correlate with Zone FCS23, which includes the subzones FCS23a and FCS23b. The faunal evidence show that the FCS23a Subzone extends to a lower stratigraphic level in M-1 0X than in E-5X. Additional microfaunal events makes it possible to enhance the biostratigraphic resolution within the Upper Maastrichtian interval. The K-T boundary is characterised by a hardground, which marks the presence of a basal Danian hiatus in both wells. This hiatus spans the Danian zones PO and Pa in M-1 0X, and P0, Pa and P1 a in E5-X. The lower part of the overlying Danian sediments correlates with Subzone P1a and P1b in M-10X and Subzone P1 b and P1c in E-5X. (au)

  16. Transcriptomic Profiling of Diverse Aedes aegypti Strains Reveals Increased Basal-level Immune Activation in Dengue Virus-refractory Populations and Identifies Novel Virus-vector Molecular Interactions

    Science.gov (United States)

    Sim, Shuzhen; Jupatanakul, Natapong; Ramirez, José L.; Kang, Seokyoung; Romero-Vivas, Claudia M.; Mohammed, Hamish; Dimopoulos, George

    2013-01-01

    Genetic variation among Aedes aegypti populations can greatly influence their vector competence for human pathogens such as the dengue virus (DENV). While intra-species transcriptome differences remain relatively unstudied when compared to coding sequence polymorphisms, they also affect numerous aspects of mosquito biology. Comparative molecular profiling of mosquito strain transcriptomes can therefore provide valuable insight into the regulation of vector competence. We established a panel of A. aegypti strains with varying levels of susceptibility to DENV, comprising both laboratory-maintained strains and field-derived colonies collected from geographically distinct dengue-endemic regions spanning South America, the Caribbean, and Southeast Asia. A comparative genome-wide gene expression microarray-based analysis revealed higher basal levels of numerous immunity-related gene transcripts in DENV-refractory mosquito strains than in susceptible strains, and RNA interference assays further showed different degrees of immune pathway contribution to refractoriness in different strains. By correlating transcript abundance patterns with DENV susceptibility across our panel, we also identified new candidate modulators of DENV infection in the mosquito, and we provide functional evidence for two potential DENV host factors and one potential restriction factor. Our comparative transcriptome dataset thus not only provides valuable information about immune gene regulation and usage in natural refractoriness of mosquito populations to dengue virus but also allows us to identify new molecular interactions between the virus and its mosquito vector. PMID:23861987

  17. Planning High-Risk High-Reward Activities.

    NARCIS (Netherlands)

    Casault, Sébastien

    2014-01-01

    This body of work addresses a gap in financial and economic theories related to assets that are typically associated with high uncertainty. Specifically, this thesis provides some foundational work towards a new way to quantify and explain how high-risk high-reward activities, such as exploration,

  18. Lacustrine Basal Ages Constrain the Last Deglaciation in the Uinta Mountains, Utah, USA

    Science.gov (United States)

    Munroe, Jeffrey; Laabs, Benjamin

    2013-04-01

    Basal radiocarbon ages from 21 high-elevation lakes limit the timing of final Pleistocene deglaciation in the Uinta Mountains of northeastern Utah, USA. The lakes are located in glacial valleys and cirques 5 to 20 km upstream from LGM terminal moraines at elevations from 2830 to 3475 m. Many are impounded behind recessional moraines. Cores were retrieved from a floating platform with a percussion corer driven to the point of refusal. All penetrated inorganic silty clay beneath gyttja. AMS radiocarbon analyses were made on terrestrial macrofossils, daphnia ephippia, pollen concentrates, and bulk sediment retrieved from the base of each core. No radiocarbon reservoir effect was observed when bulk dates were checked against terrestrial material. Radiocarbon results were converted to calendar years using the IntCal09 calibration curve in OxCal 4.1. Given the stratigraphy observed in the cores, these calibrated basal ages are considered close limits on the timing of the local deglaciation and lake formation. The oldest three lakes have basal radiocarbon ages that calibrate to a few centuries after the Bölling/Alleröd warming, indicating that the landscape was becoming ice free at this time. These are followed by an overlapping group of five lakes with basal ages between 13.5 and 13.0 ka BP. Five more cores, from four separate lakes, have basal ages tightly clustered between 13.0 and 12.5 ka BP. Three of these lakes are dammed by moraines, suggesting glacial activity during the early part of the Younger Dryas interval. The lone kettle lake in the study yielded a basal age of 12.3 ka BP, considerably younger than the basal age of 13.9 ka BP from a nearby lake filling a bedrock basin, indicating that buried ice may have been locally stable for more than a millennium after deglaciation. The remaining seven lakes have basal ages between 12.0 and 11.0 ka BP. Four of these lakes are also dammed by moraines. These two non-overlapping clusters of basal ages for moraine

  19. Modeling the basal dynamics of p53 system.

    Directory of Open Access Journals (Sweden)

    Tingzhe Sun

    Full Text Available BACKGROUND: The tumor suppressor p53 has become one of most investigated genes. Once activated by stress, p53 leads to cellular responses such as cell cycle arrest and apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: Most previous models have ignored the basal dynamics of p53 under nonstressed conditions. To explore the basal dynamics of p53, we constructed a stochastic delay model by incorporating two negative feedback loops. We found that protein distribution of p53 under nonstressed condition is highly skewed with a fraction of cells showing high p53 levels comparable to those observed under stressed conditions. Under nonstressed conditions, asynchronous and spontaneous p53 pulses are triggered by basal DNA double strand breaks produced during normal cell cycle progression. The first peaking times show a predominant G1 distribution while the second ones are more widely distributed. The spontaneous pulses are triggered by an excitable mechanism. Once initiated, the amplitude and duration of pulses remain unchanged. Furthermore, the spontaneous pulses are filtered by ataxia telangiectasia mutated protein mediated posttranslational modifications and do not result in substantial p21 transcription. If challenged by externally severe DNA damage, cells generate synchronous p53 pulses and induce significantly high levels of p21. The high expression of p21 can also be partially induced by lowering the deacetylation rate. CONCLUSIONS: Our results demonstrated that the dynamics of p53 under nonstressed conditions is initiated by an excitable mechanism and cells become fully responsive only when cells are confronted with severe damage. These findings advance our understanding of the mechanism of p53 pulses and unlock many opportunities to p53-based therapy.

  20. High effective silica fume alkali activator

    Indian Academy of Sciences (India)

    Vladimír Živica

    2004-04-01

    Growing demands on the engineering properties of cement based materials and the urgency to decrease unsuitable ecologic impact of Portland cement manufacturing represent significant motivation for the development of new cement corresponding to these aspects. One category represents prospective alkali activated cements. A significant factor influencing their properties is alkali activator used. In this paper we present a new high effective alkali activator prepared from silica fume and its effectiveness. According to the results obtained this activator seems to be more effective than currently used activators like natrium hydroxide, natrium carbonate, and water glass.

  1. Cholinergic modulation differs between basal and apical dendritic excitation of hippocampal CA1 pyramidal cells.

    Science.gov (United States)

    Leung, L Stan; Péloquin, Pascal

    2010-08-01

    We hypothesize that endogenous cholinergic modulation of dendritic processing of hippocampal CA1 is layer specific, and it specifically enhances spike output resulting from basal as compared with the apical dendritic excitation. Laminar profiles of evoked field potentials were recorded in the CA1 area of urethane-anesthetized rats using multichannel silicon probes and analyzed as current source density. High-frequency stimulation of the pontis oralis (PnO) attenuated the midapical more than the basal or distal apical dendritic excitatory sink. Population spike (PS) and excitatory sink-PS potentiation resulting from basal dendritic excitation were facilitated, while the PS evoked by apical dendritic stimulation was attenuated by PnO stimulation. Perfusion of cholinergic agonist carbachol onto hippocampal slices in vitro also attenuated the apical more than the basal dendritic excitatory postsynaptic potentials. Excitatory sink attenuation and PS changes after PnO stimulation were blocked by systemic or local scopolamine and by intracerebroventricular (icv) M1 receptor antagonist pirenzepine but not by icv M2 receptor antagonist AFDX-116 or nicotinic antagonists. However, a hippocampal theta rhythm activated by PnO stimulation was blocked by systemic but not by local scopolamine. We conclude that endogenous acetylcholine mediates a stronger presynaptic inhibition of the midapical than basal and distal apical excitation mainly through M1 receptors.

  2. Basal Organelles of Bacterial Flagella

    Science.gov (United States)

    Cohen-Bazire, Germaine; London, Jack

    1967-01-01

    Liberated by enzymatic lysis of the cells, the flagella of Rhodospirillum rubrum, R. molischianum, and R. fulvum all have a similar structure. The hook at the base of the flagellum is connected by a short, narrow collar to a paired disc in the basal organelle. This paired disc is in turn connected to a second paired disc. The disposition of flagella to which fragments of the cell membrane still adhere suggests that the narrow collar at the base of the hook traverses both the wall and the membrane, and that the upper pair of discs in the basal organelle lies just beneath the surface of the membrane. Images PMID:6039362

  3. 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

  4. A high isoflavone diet decreases 5' adenosine monophosphate-activated protein kinase activation and does not correct selenium-induced elevations in fasting blood glucose in mice.

    Science.gov (United States)

    Stallings, Michael T; Cardon, Brandon R; Hardman, Jeremy M; Bliss, Tyler A; Brunson, Scott E; Hart, Chris M; Swiss, Maria D; Hepworth, Squire D; Christensen, Merrill J; Hancock, Chad R

    2014-04-01

    Selenium (Se) has been implicated as a micronutrient that decreases adenosine monophosphate-activated protein kinase (AMPK) signaling and may increase diabetes risk by reducing insulin sensitivity. Soy isoflavones (IF) are estrogen-like compounds that have been shown to attenuate insulin resistance, hyperglycemia, adiposity, and increased AMPK activation. We hypothesized that a high IF (HIF) diet would prevent the poor metabolic profile associated with high Se intake. The purpose of this study was to examine changes in basal glucose metabolism and AMPK signaling in response to an HIF diet and/or supplemental Se in a mouse model. Male FVB mice were divided into groups receiving either a control diet with minimal IF (low IF) or an HIF diet. Each dietary group was further subdivided into groups receiving either water or Se at a dose of 3 mg Se/kg body weight daily, as Se-methylselenocysteine (SMSC). After 5 months, mice receiving SMSC had elevated fasting glucose (P < .05) and a tendency for glucose intolerance (P = .08). The increase in dietary IF did not result in improved fasting blood glucose. Interestingly, after 6 months, HIF-fed mice had decreased basal AMPK activation in liver and skeletal muscle tissue (P < .05). Basal glucose metabolism was changed by SMSC supplementation as evidenced by increased fasting blood glucose and glucose intolerance. High dietary IF levels did not protect against aberrant blood glucose. In FVB mice, decreased basal AMPK activation is not the mechanism through which Se exerts its effect. These results suggest that more research must be done to elucidate the role of Se and IF in glucose metabolism.

  5. Reduced basal and novelty-induced levels of activity-regulated cytoskeleton associated protein (Arc) and c-Fos mRNA in the cerebral cortex and hippocampus of APPswe/PS1ΔE9 transgenic mice.

    Science.gov (United States)

    Christensen, Ditte Z; Thomsen, Morten S; Mikkelsen, Jens D

    2013-07-01

    Activity-regulated cytoskeletal-associated protein (Arc) and c-Fos are immediate early gene (IEG) products induced by novelty in the hippocampus and involved in the consolidation of synaptic plasticity and long-term memory. We investigated whether induction of arc and c-fos after exposure to a novel open field environment was compromised in different neocortical areas and the hippocampal formation in APP/PS1ΔE9 transgenic mice characterized by pronounced accumulation and deposition of beta amyloid (Aβ). Notably, the basal level of Arc and c-fos mRNA in the neocortex was significantly lower in APP/PS1ΔE9 compared to wild-type mice. Novelty exposure induced an increase in Arc and c-Fos mRNA in the medial prefrontal cortex (mPFC), parietal cortex, and hippocampal formation in both APP/PS1ΔE9 transgenic and wild-type mice. However, novelty-induced IEG expression did not reach the same levels in APP/PS1ΔE9 as in the wild-type mice. In contrast, synaptophysin levels did not differ between mutant and wild type mice, suggesting that the observed effect was not due to a general decrease in the number of presynapses. These data suggest a reduction in basal and novelty-induced neuronal activity in a transgenic mouse model of Alzheimer's disease, which is most pronounced in cortical regions, indicating that a decreased functional response in IEG expression could be partly responsible for the cognitive deficits observed in patients with Alzheimer's disease.

  6. Motor control in basal ganglia circuits using fMRI and brain atlas approaches.

    Science.gov (United States)

    Lehéricy, Stéphane; Bardinet, Eric; Tremblay, Leon; Van de Moortele, Pierre-Francois; Pochon, Jean-Baptiste; Dormont, Didier; Kim, Dae-Shik; Yelnik, Jerome; Ugurbil, Kamil

    2006-02-01

    In this study, we examined how the motor, premotor and associative basal ganglia territories process movement parameters such as the complexity and the frequency of movement. Twelve right-handed volunteers were studied using EPI BOLD contrast (3 T) while performing audio-paced finger tapping tasks designed to differentiate basal ganglia territories. Tasks varied movement complexity (repetitive index tapping, simple sequence of finger movements and complex sequence of 10 moves) and frequency (from 0.5 to 3 Hz). Activation maps were coregistered onto a 3-D brain atlas derived from post-mortem brains. Three main patterns of activation were observed. In the posterior putamen and the sensorimotor cortex, signal increased with movement frequency but not with movement complexity. In premotor areas, the anterior putamen and the ventral posterolateral thalamus, signal increased regularly with increasing movement frequency and complexity. In rostral frontal areas, the caudate nucleus, the subthalamic nucleus and the ventral anterior/ventrolateral thalamus, signal increased mainly during the complex task and the high frequency task (3 Hz). These data show the different roles of motor, premotor and associative basal ganglia circuits in the processing of motor-related operations and suggest that activation can be precisely located within the entire circuitry of the basal ganglia.

  7. The Sal-like 4 - integrin α6β1 network promotes cell migration for metastasis via activation of focal adhesion dynamics in basal-like breast cancer cells.

    Science.gov (United States)

    Itou, Junji; Tanaka, Sunao; Li, Wenzhao; Iida, Atsuo; Sehara-Fujisawa, Atsuko; Sato, Fumiaki; Toi, Masakazu

    2017-01-01

    During metastasis, cancer cell migration is enhanced. However, the mechanisms underlying this process remain elusive. Here, we addressed this issue by functionally analyzing the transcription factor Sal-like 4 (SALL4) in basal-like breast cancer cells. Loss-of-function studies of SALL4 showed that this transcription factor is required for the spindle-shaped morphology and the enhanced migration of cancer cells. SALL4 also up-regulated integrin gene expression. The impaired cell migration observed in SALL4 knockdown cells was restored by overexpression of integrin α6 and β1. In addition, we clarified that integrin α6 and β1 formed a heterodimer. At the molecular level, loss of the SALL4 - integrin α6β1 network lost focal adhesion dynamics, which impairs cell migration. Over-activation of Rho is known to inhibit focal adhesion dynamics. We observed that SALL4 knockdown cells exhibited over-activation of Rho. Aberrant Rho activation was suppressed by integrin α6β1 expression, and pharmacological inhibition of Rho activity restored cell migration in SALL4 knockdown cells. These results indicated that the SALL4 - integrin α6β1 network promotes cell migration via modulation of Rho activity. Moreover, our zebrafish metastasis assays demonstrated that this gene network enhances cell migration in vivo. Our findings identify a potential new therapeutic target for the prevention of metastasis, and provide an improved understanding of cancer cell migration. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Cryotherapy in basal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Sandra A

    1999-01-01

    Full Text Available Cryotherapy has proved to be an effective tool in the management of various dermatoses. We report 6 patients with histopathologically proven basal cell carcinoma of variable sizes treated with liquid nitrogen cryotherapy by the open spray technique. Lesions tended to heal with depigmentation and scar formation. However depigmented areas often repigmented over a period of time.

  9. Mephedrone alters basal ganglia and limbic dynorphin systems.

    Science.gov (United States)

    German, Christopher L; Alburges, Mario E; Hoonakker, Amanda J; Fleckenstein, Annette E; Hanson, Glen R

    2014-08-25

    Mephedrone (4-methymethcathinone) is a synthetic cathinone designer drug that disrupts central nervous system (CNS) dopamine (DA) signaling. Numerous central neuropeptide systems reciprocally interact with dopaminergic neurons to provide regulatory counterbalance, and are altered by aberrant DA activity associated with stimulant exposure. Endogenous opioid neuropeptides are highly concentrated within dopaminergic CNS regions and facilitate many rewarding and aversive properties associated with drug use. Dynorphin, an opioid neuropeptide and kappa receptor agonist, causes dysphoria and aversion to drug consumption through signaling within the basal ganglia and limbic systems, which is affected by stimulants. This study evaluated how mephedrone alters basal ganglia and limbic system dynorphin content, and the role of DA signaling in these changes. Repeated mephedrone administrations (4 × 25 mg/kg/injection, 2-h intervals) selectively increased dynorphin content throughout the dorsal striatum and globus pallidus, decreased dynorphin content within the frontal cortex, and did not alter dynorphin content within most limbic system structures. Pretreatment with D1 -like (SCH-23380) or D2 -like (eticlopride) antagonists blocked mephedrone-induced changes in dynorphin content in most regions examined, indicating altered dynorphin activity is a consequence of excessive DA signaling. Synapse, 2014. © 2014 Wiley Periodicals, Inc.

  10. Cognitive-motor interactions of the basal ganglia in development

    OpenAIRE

    Gerry eLeisman; Orit eBraun-Benjamin; Robert eMelillo

    2014-01-01

    Neural circuits linking activity in anatomically segregated populations of neurons in subcortical structures and the neocortex throughout the human brain regulate complex behaviors such as walking, talking, language comprehension, and other cognitive functions associated with frontal lobes. The basal ganglia, which regulate motor control, are also crucial elements in the circuits that confer human reasoning and adaptive function. The basal ganglia are key elements in the control of reward-bas...

  11. CB1 Cannabinoid Receptor-Dependent Activation of mTORC1/Pax6 Signaling Drives Tbr2 Expression and Basal Progenitor Expansion in the Developing Mouse Cortex.

    Science.gov (United States)

    Díaz-Alonso, Javier; Aguado, Tania; de Salas-Quiroga, Adán; Ortega, Zaira; Guzmán, Manuel; Galve-Roperh, Ismael

    2015-09-01

    The CB1 cannabinoid receptor regulates cortical progenitor proliferation during embryonic development, but the molecular mechanism of this action remains unknown. Here, we report that CB1-deficient mouse embryos show premature cell cycle exit, decreased Pax6- and Tbr2-positive cell number, and reduced mammalian target of rapamycin complex 1 (mTORC1) activation in the ventricular and subventricular cortical zones. Pharmacological stimulation of the CB1 receptor in cortical slices and progenitor cell cultures activated the mTORC1 pathway and increased the number of Pax6- and Tbr2-expressing cells. Likewise, acute CB1 knockdown in utero reduced mTORC1 activation and cannabinoid-induced Tbr2-positive cell generation. Luciferase reporter and chromatin immunoprecipitation assays revealed that the CB1 receptor drives Tbr2 expression downstream of Pax6 induction in an mTORC1-dependent manner. Altogether, our results demonstrate that the CB1 receptor tunes dorsal telencephalic progenitor proliferation by sustaining the transcriptional activity of the Pax6-Tbr2 axis via the mTORC1 pathway, and suggest that alterations of CB1 receptor signaling, by producing the missexpression of progenitor identity determinants may contribute to neurodevelopmental alterations.

  12. The prolyl isomerase Pin1 acts synergistically with CDK2 to regulate the basal activity of estrogen receptor α in breast cancer.

    Directory of Open Access Journals (Sweden)

    Chiara Lucchetti

    Full Text Available In hormone receptor-positive breast cancers, most tumors in the early stages of development depend on the activity of the estrogen receptor and its ligand, estradiol. Anti-estrogens, such as tamoxifen, have been used as the first line of therapy for over three decades due to the fact that they elicit cell cycle arrest. Unfortunately, after an initial period, most cells become resistant to hormonal therapy. Peptidylprolyl isomerase 1 (Pin1, a protein overexpressed in many tumor types including breast, has been demonstrated to modulate ERalpha activity and is involved in resistance to hormonal therapy. Here we show a new mechanism through which CDK2 drives an ERalpha-Pin1 interaction under hormone- and growth factor-free conditions. The PI3K/AKT pathway is necessary to activate CDK2, which phosphorylates ERalphaSer294, and mediates the binding between Pin1 and ERalpha. Site-directed mutagenesis demonstrated that ERalphaSer294 is essential for Pin1-ERalpha interaction and modulates ERalpha phosphorylation on Ser118 and Ser167, dimerization and activity. These results open up new drug treatment opportunities for breast cancer patients who are resistant to anti-estrogen therapy.

  13. Enclosure for handling high activity materials

    Energy Technology Data Exchange (ETDEWEB)

    Jimeno de Osso, F.

    1977-07-01

    One of the most important problems that are met at the laboratories producing and handling radioisotopes is that of designing, building and operating enclosures suitable for the safe handling of active substances. With this purpose in mind, an enclosure has been designed and built for handling moderately high activities under a shielding made of 150 mm thick lead. In this report a description is given of those aspects that may be of interest to people working in this field. (Author)

  14. Basal hydraulic conditions of Ice Stream B

    Science.gov (United States)

    Engelhardt, Hermann; Kamb, Barclay

    1993-01-01

    Fifteen boreholes have been drilled to the base of Ice Stream B in the vicinity of UpB Camp. The boreholes are spread over an area of about 500 x 1000 m. Several till cores were retrieved from the bottom of the 1000-m-deep holes. Laboratory tests using a simple shear box revealed a yield strength of basal till of 2 kPa. This agrees well with in-situ measurements using a shear vane. Since the average basal shear stress of Ice Stream B with a surface slope of 0.1 degree is about 20 kPa, the ice stream cannot be supported by till that weak. Additional support for this conclusion comes from the basal water pressure that has been measured in all boreholes as soon as the hot water drill reached bottom. In several boreholes, the water pressure has been continuously monitored; in two of them, over several years. The water pressure varies but stays within 1 bar of flotation where ice overburden pressure and water pressure are equal. The ratio of water and overburden pressure lies between 0.986 and 1.002. This is an extremely high value as compared to other fast-moving ice masses; e.g., Variegated Glacier in surge has a ratio of 0.8, and Columbia Glacier - a fast-moving tidewater glacier - has a ratio of 0.9. It implies that water flow under the glacier occurs in a thin film and not in conduits that would drain away water too rapidly. It also implies that basal sliding must be very effective. Water flow under the glacier was measured in a salt-injection experiment where a salt pulse was released at the bottom of a borehole while 60 m down-glacier, the electrical resistance was measured between two other boreholes. A flow velocity of 7 mm/s was obtained.

  15. [The action of émoksipin on the basal activity of cyclic nucleotide phosphodiesterase and on the late receptor potential of the isolated retina].

    Science.gov (United States)

    Shvedova, A A; Polianskiĭ, N B; Akopian, G Kh; Dzhafarov, A I

    1989-09-01

    The influence of emoxypin (derivate of 3-hydroxypyridine) upon the late receptor potential (LRP) and activity of the cyclic 3',5'-nucleotide phosphodiesterase (PDE) have been investigated. The inhibition of PDE and increase of the amplitude of LPR have been shown. The curve (RP as a function of the stimulus light intensity) was moved towards the lesser lighting and the time of the achievement of the maximum was increased. Thus, emoxypin produces an effect on the LRP like classical inhibitors of PDE. It is suggested that increase of the functional activity of the retinae upon the influence of emoxypin in caused by the influence of the one towards the system of the cyclic nucleotides.

  16. Hydrolytic activity toward pyridoxine-5'-beta-D-glucoside in rat intestinal mucosa is not increased by vitamin B-6 deficiency: effect of basal diet composition and pyridoxine intake.

    Science.gov (United States)

    Mackey, Amy D; Lieu, Siam O; Carman, Catherine; Gregory, Jesse F

    2003-05-01

    Pyridoxine-5'-beta-D-glucoside (PNG), a glycosylated form of dietary vitamin B-6, is partially hydrolyzed in the small intestine by the cytosolic enzyme pyridoxine-5'-beta-D-glucoside hydrolase (PNG hydrolase) and by the brush border enzyme lactase phlorizin hydrolase (LPH) to release free pyridoxine (PN). This laboratory has previously shown that PNG hydrolase activity is inversely related to dietary vitamin B-6 in rats and guinea pigs. The current investigation was done to examine the effect of dietary PN on PNG hydrolytic activity and its distribution. Nutrient compositional differences between the AIN-76A and AIN-93G purified diets that were unrelated to vitamin B-6 were also examined in relation to PNG hydrolysis in rat small intestinal mucosa. Study one included rats (n = 29) that were fed the AIN-93G diet providing a range of PN concentrations for 5 wk. Rats (n = 49) in study two were fed either AIN-76A or AIN-93G each with graded concentrations of PN. In both studies, rat growth and plasma and liver pyridoxal 5'-phosphate (PLP) concentrations increased (P < 0.05) with increasing concentrations of dietary PN. PNG hydrolytic activity localized to the brush border membrane was five times that measured in the cytosol. Cytosolic PNG hydrolytic activity increased significantly with increasing dietary PN concentration in rats fed the AIN-76A, but not AIN-93G diet. Activity in the mucosal total membrane fraction did not increase in proportion to dietary PN concentration for either diet. Regardless of dietary PN concentration, the basal nutrient composition of the diets affected growth and PNG hydrolytic activity in intestinal mucosa. In contrast to previous results from this laboratory, intestinal hydrolytic activity toward PNG did not increase in vitamin B-6-deficient rats.

  17. Phenolic indeno[1,2-b]indoles as ABCG2-selective potent and non-toxic inhibitors stimulating basal ATPase activity.

    Science.gov (United States)

    Gozzi, Gustavo Jabor; Bouaziz, Zouhair; Winter, Evelyn; Daflon-Yunes, Nathalia; Honorat, Mylène; Guragossian, Nathalie; Marminon, Christelle; Valdameri, Glaucio; Bollacke, Andre; Guillon, Jean; Pinaud, Noël; Marchivie, Mathieu; Cadena, Silvia M; Jose, Joachim; Le Borgne, Marc; Di Pietro, Attilio

    2015-01-01

    Ketonic indeno[1,2-b]indole-9,10-dione derivatives, initially designed as human casein kinase II (CK2) inhibitors, were recently shown to be converted into efficient inhibitors of drug efflux by the breast cancer resistance protein ABCG2 upon suited substitutions including a N (5)-phenethyl on C-ring and hydrophobic groups on D-ring. A series of ten phenolic and seven p-quinonic derivatives were synthesized and screened for inhibition of both CK2 and ABCG2 activities. The best phenolic inhibitors were about threefold more potent against ABCG2 than the corresponding ketonic derivatives, and showed low cytotoxicity. They were selective for ABCG2 over both P-glycoprotein and MRP1 (multidrug resistance protein 1), whereas the ketonic derivatives also interacted with MRP1, and they additionally displayed a lower interaction with CK2. Quite interestingly, they strongly stimulated ABCG2 ATPase activity, in contrast to ketonic derivatives, suggesting distinct binding sites. In contrast, the p-quinonic indenoindoles were cytotoxic and poor ABCG2 inhibitors, whereas a partial inhibition recovery could be reached upon hydrophobic substitutions on D-ring, similarly to the ketonic derivatives.

  18. High-activity liquid packaging design criteria

    Energy Technology Data Exchange (ETDEWEB)

    1994-05-01

    In recent studies, it has been acknowledged that there is an emerging need for packaging to transport high-activity liquid off the Hanford Site to support characterization and process development activities of liquid waste stored in underground tanks. These studies have dealt with specimen testing needs primarily at the Hanford Site; however, similar needs appear to be developing at other US Department of Energy (DOE) sites. The need to ship single and multiple specimens to offsite laboratories is anticipated because it is predicted that onsite laboratories will be overwhelmed by an increasing number and size (volume) of samples. Potentially, the specimen size could range from 250 mL to greater than 50 L. Presently, no certified Type-B packagings are available for transport of high-activity liquid radioactive specimens in sizes to support Site missions.

  19. Basal cell carcinomas in elderly patients treated by cryotherapy.

    Science.gov (United States)

    Chiriac, Anca; Mihaila, Doina; Foia, Liliana; Solovan, Caius

    2013-01-01

    Basal cell carcinoma is a malignant skin tumor with high incidence in our country, especially in rural areas, on sun-exposed skin (particularly on the face) in elderly patients. We present three cases of basal cell carcinoma with good results with cryotherapy. This report aims to outline and to prove that in some difficult situations, a simple, inexpensive, easy-to-perform procedure with no contraindications and with minimal side effects (erythema, mild pain) can be applied and resolve such cases.

  20. High activity carbon sorbents for mercury capture

    Energy Technology Data Exchange (ETDEWEB)

    George G. Stavropoulos; Irene S. Diamantopoulou; George E. Skodras; George P. Sakellaropoulos [Aristotle University of Thessaloniki, Thessaloniki (Greece). Chemical Process Engineering Laboratory

    2006-07-01

    High efficiency activated carbons have been prepared for removing mercury from gas streams. Starting materials used were petroleum coke, lignite, charcoal and olive seed waste, and were chemically activated with KOH. Produced adsorbents were primarily characterized for their porosity by N{sub 2} adsorption at 77K. Their mercury retention capacity was characterized based on the breakthrough curves. Compared with typical commercial carbons, they have exhibited considerably enhanced mercury adsorption capacity. An attempt has been made to correlate mercury entrapment and pore structure. It has been shown that physical surface area is increased during activation in contrast to the mercury adsorption capacity that initially increases and tends to decrease at latter stages. Desorption of active sites may be responsible for this behavior. 10 refs., 3 figs., 1 tab.

  1. Met induces diverse mammary carcinomas in mice and is associated with human basal breast cancer

    OpenAIRE

    Graveel, Carrie R.; DeGroot, Jack D.; Su, Yanli; Koeman, Julie; Dykema, Karl; Leung, Samuel; Snider, Jacqueline; Davies, Sherri R.; Swiatek, Pamela J.; Cottingham, Sandra; Watson, Mark A.; Matthew J Ellis; Sigler, Robert E.; Furge, Kyle A.; Vande Woude, George F

    2009-01-01

    Understanding the signaling pathways that drive aggressive breast cancers is critical to the development of effective therapeutics. The oncogene MET is associated with decreased survival in breast cancer, yet the role that MET plays in the various breast cancer subtypes is unclear. We describe a knockin mouse with mutationally activated Met (Metmut) that develops a high incidence of diverse mammary tumors with basal characteristics, including metaplasia, absence of progesterone receptor and E...

  2. Role of high-field intraoperative magnetic resonance imaging on a multi-image fusion-guided stereotactic biopsy of the basal ganglia: A case report.

    Science.gov (United States)

    Sun, Xiang; Chen, Zhijuan; Yang, Shuyuan; Zhang, Jianning; Yue, Shuyuan; Wang, Zengguang; Yang, Weidong

    2015-01-01

    The aim of the present case study was to investigate the advantages of intraoperative magnetic resonance imaging (iMRI) on the real-time guidance and monitoring of a stereotactic biopsy. The study describes a patient with intracranial lesions, which were examined by conventional MRI and diffusion tensor imaging using a 1.5T intraoperative MRI system. The digital and pre-operative positron emission/computed tomography image data were transferred to a BrainLAB planning workstation, and a variety of images were automatically fused. The BrainLAB software was then used to reconstruct the corticospinal tract (CST) and create a three-dimensional display of the anatomical association between the CST and the brain lesions. A Leksell surgical planning workstation was used to identify the ideal target site and a reasonable needle track for the biopsy. The 1.5T iMRI was used to effectively monitor the intracranial condition during the brain biopsy procedure. Post-operatively, the original symptoms of the patient were not aggravated and no further neurological deficits were apparent. The histopathological diagnosis of non-Hodgkin's B-cell lymphoma was made. Using high-field iMRI, the multi-image fusion-guided stereotactic brain biopsy allows for a higher positive rate of biopsy and a lower incidence of complications. The approach of combining multi-image fusion images with the frame-based stereotactic biopsy may be clinically useful for intracranial lesions of deep functional areas.

  3. Does cellular aging relate to patterns of allostasis? An examination of basal and stress reactive HPA axis activity and telomere length.

    Science.gov (United States)

    Tomiyama, A Janet; O'Donovan, Aoife; Lin, Jue; Puterman, Eli; Lazaro, Alanie; Chan, Jessica; Dhabhar, Firdaus S; Wolkowitz, Owen; Kirschbaum, Clemens; Blackburn, Elizabeth; Epel, Elissa

    2012-04-12

    Long-term exposure to stress and its physiological mediators, in particular cortisol, may lead to impaired telomere maintenance. In this study, we examine if greater cortisol responses to an acute stressor and/or dysregulated patterns of daily cortisol secretion are associated with shorter telomere length. Twenty-three postmenopausal women comprising caregivers for dementia partners (n=14) and age- and BMI-matched non-caregivers provided home sampling of cortisol-saliva samples at waking, 30 min after waking, and bedtime, and a 12-hour overnight urine collection. They were also exposed to an acute laboratory stressor throughout which they provided saliva samples. Peripheral blood mononuclear cells were isolated from a fasting blood sample and assayed for telomere length. As hypothesized, greater cortisol responses to the acute stressor were associated with shorter telomeres, as were higher overnight urinary free cortisol levels and flatter daytime cortisol slopes. While robust physiological responses to acute stress serve important functions, the long-term consequences of frequent high stress reactivity may include accelerated telomere shortening.

  4. BASAL CELL CARCINOMA IN AN UNUSUAL SITE - VULVA

    Directory of Open Access Journals (Sweden)

    Sumangala G

    2016-06-01

    Full Text Available Basal cell carcinoma (BCC is the most common malignancy of the skin, but BCC of the vulva is a rare entity. BCC of vulva accounts for less than 5% of all vulvar neoplasms and less than 1% of all basal cell carcinomas. Vulvar basal cell carcinoma has a low propensity for metastatic spread but has a high chance of local recurrence after simple excision. We report a 50- year-old woman presenting with pruritus vulva. Physical examination revealed a 2.5 x 1.5 cm hyperpigmented plaque on the left labium majus. The histopathology was consistent with superficially invasive basal cell carcinoma. The patient underwent radical local excision including the clitoris and remained disease free at postsurgical follow-up after eight months.

  5. Clomiphene Citrate Treatment Cycle Outcomes of Polycystic Ovary Syndrome Patients Based on Basal High Sensitive C-Reactive Protein Levels: A Cross-Sectional Study

    Science.gov (United States)

    Kahyaoglu, Serkan; Yumuşak, Omer Hamid; Ozyer, Sebnem; Pekcan, Meryem Kuru; Erel, Merve; Cicek, Mahmut Nedim; Erkaya, Salim; Tasci, Yasemin

    2017-01-01

    Background Polycystic ovary syndrome (PCOS) is highly associated with an ovulatory infertility, features of the metabolic syndrome, including obesity, insulin resistance and dyslipidemia. Serum concentrations of high sensitive C-reactive protein (hs-CRP) were significantly higher in obese than in non-obese PCOS patients at baseline, suggesting a relationship between elevated hs-CRP levels and obesity. The aim of this study was to evaluate whether cycle day 3 hs-CRP levels before clomiphene citrate (CC) treatment would predict cycle outcomes in women with PCOS. Materials and Methods This cross-sectional study was conducted among 84 infertile women with PCOS who were treated with CC at Zekai Tahir Burak Women’s Health Education and Research Hospital, Ankara, Turkey, between January 2014 and January 2015. Based on the exclusion criteria, cycle outcomes of remaining 66 infertile women with PCOS treated with CC were analyzed. The hs-CRP levels and insulin resistance indexes were evaluated on day 3 of the CC treatment cycle. The primary outcome measures were number of preovulatory follicles measuring≥17 mm and pregnancy rates. Results The mean ± SD age of the patients was 24.0 ± 3.8 years (range 18-36). The mean ± SD body mass index (BMI) of the patients was 25.7 ± 4.9 (range 17-43). Fifty patients developed dominant follicle (75%) and 5 patients established clinical pregnancy during the study (clinical pregnancy rate: 7%). The mean ± SD baseline hs-CRP, fasting insulin and Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) values of the patients with and without dominant follicle generation during treatment cycle were 6.42 ± 7.05 and 4.41 ± 2.95 (P=0.27), 11.61 ± 6.94 and 10.95 ± 5.65 (P=0.73), 2.68 ± 1.79 and 2.41 ± 1.30 (P=0.58), respectively. The mean ± SD baseline hs-CRP, fasting insulin and HOMA-IR values of the patients with and without clinical pregnancy establishment following treatment cycle were 6.30 ± 2.56 and 5.90 ± 6.57 (P=0.89), 11

  6. Clomiphene Citrate Treatment Cycle Outcomes of Polycystic Ovary Syndrome Patients Based on Basal High Sensitive C-Reactive Protein Levels: A Cross-Sectional Study

    Directory of Open Access Journals (Sweden)

    Serkan Kahyaoglu

    2016-11-01

    Full Text Available Background: Polycystic ovary syndrome (PCOS is highly associated with an ovulatory infertility, features of the metabolic syndrome, including obesity, insulin resistance and dyslipidemia. Serum concentrations of high sensitive C-reactive protein (hs-CRP were significantly higher in obese than in non-obese PCOS patients at baseline, suggesting a relationship between elevated hs-CRP levels and obesity. The aim of this study was to evaluate whether cycle day 3 hs-CRP levels before clomiphene citrate (CC treatment would predict cycle outcomes in women with PCOS. Materials and Methods: This cross-sectional study was conducted among 84 infertile women with PCOS who were treated with CC at Zekai Tahir Burak Women’s Health Education and Research Hospital, Ankara, Turkey, between January 2014 and January 2015. Based on the exclusion criteria, cycle outcomes of remaining 66 infertile women with PCOS treated with CC were analyzed. The hs-CRP levels and insulin resistance indexes were evaluated on day 3 of the CC treatment cycle. The primary outcome measures were number of preovulatory follicles measuring≥17 mm and pregnancy rates. Results: The mean ± SD age of the patients was 24.0 ± 3.8 years (range 18-36. The mean ± SD body mass index (BMI of the patients was 25.7 ± 4.9 (range 17-43. Fifty patients developed dominant follicle (75% and 5 patients established clinical pregnancy during the study (clinical pregnancy rate: 7%. The mean ± SD baseline hs-CRP, fasting insulin and Homeostasis Model Assessment-Insulin Resistance (HOMA-IR values of the patients with and without dominant follicle generation during treatment cycle were 6.42 ± 7.05 and 4.41 ± 2.95 (P=0.27, 11.61 ± 6.94 and 10.95 ± 5.65 (P=0.73, 2.68 ± 1.79 and 2.41 ± 1.30 (P=0.58, respectively. The mean ± SD baseline hs-CRP, fasting insulin and HOMA-IR values of the patients with and without clinical pregnancy establishment following treatment cycle were 6.30 ± 2.56 and 5.90 ± 6

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

    Directory of Open Access Journals (Sweden)

    E. C. Lawson

    2015-08-01

    Full Text Available 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

  8. 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

  9. An MRI atlas of the mouse basal ganglia.

    Science.gov (United States)

    Ullmann, Jeremy F P; Watson, Charles; Janke, Andrew L; Kurniawan, Nyoman D; Paxinos, George; Reutens, David C

    2014-07-01

    The basal ganglia are a group of subpallial nuclei that play an important role in motor, emotional, and cognitive functions. Morphological changes and disrupted afferent/efferent connections in the basal ganglia have been associated with a variety of neurological disorders including psychiatric and movement disorders. While high-resolution magnetic resonance imaging has been used to characterize changes in brain structure in mouse models of these disorders, no systematic method for segmentation of the C57BL/6 J mouse basal ganglia exists. In this study we have used high-resolution MR images of ex vivo C57BL/6 J mouse brain to create a detailed protocol for segmenting the basal ganglia. We created a three-dimensional minimum deformation atlas, which includes the segmentation of 35 striatal, pallidal, and basal ganglia-related structures. In addition, we provide mean volumes, mean T2 contrast intensities and mean FA and ADC values for each structure. This MR atlas is available for download, and enables researchers to perform automated segmentation in genetic models of basal ganglia disorders.

  10. Production of high specific activity silicon-32

    Energy Technology Data Exchange (ETDEWEB)

    Phillips, D.R. [Los Alamos National Lab., NM (United States); Brzezinski, M.A. [Univ. of California, Santa Barbara, CA (United States). Marine Biotechnology Center

    1998-12-31

    This is the final report of a three-year, Laboratory Directed Research and Development Project (LDRD) at Los Alamos National Laboratory (LANL). There were two primary objectives for the work performed under this project. The first was to take advantage of capabilities and facilities at Los Alamos to produce the radionuclide {sup 32}Si in unusually high specific activity. The second was to combine the radioanalytical expertise at Los Alamos with the expertise at the University of California to develop methods for the application of {sup 32}Si in biological oceanographic research related to global climate modeling. The first objective was met by developing targetry for proton spallation production of {sup 32}Si in KCl targets and chemistry for its recovery in very high specific activity. The second objective was met by developing a validated field-useable, radioanalytical technique, based upon gas-flow proportional counting, to measure the dynamics of silicon uptake by naturally occurring diatoms.

  11. The human airway epithelial basal cell transcriptome.

    Directory of Open Access Journals (Sweden)

    Neil R Hackett

    Full Text Available BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSION/SIGNIFICANCE: The human airway epithelial basal cell signature identified in the present study provides novel insights into the molecular phenotype and biology of

  12. Active vibration isolation of high precision machines

    CERN Document Server

    Collette, C; Artoos, K; Hauviller, C

    2010-01-01

    This paper provides a review of active control strategies used to isolate high precisionmachines (e.g. telescopes, particle colliders, interferometers, lithography machines or atomic force microscopes) from external disturbances. The objective of this review is to provide tools to develop the best strategy for a given application. Firstly, the main strategies are presented and compared, using single degree of freedom models. Secondly, the case of huge structures constituted of a large number of elements, like particle colliders or segmented telescopes, is considered.

  13. Movement of basal plane dislocations in GaN during electron beam irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Yakimov, E. B. [Institute of Microelectronics Technology and High Purity Materials, Russian Academy of Science, 6, Academician Ossipyan str., Chernogolovka, Moscow Region 142432 (Russian Federation); National University of Science and Technology MISiS, Leninskiy pr. 4, Moscow 119049 (Russian Federation); Vergeles, P. S. [Institute of Microelectronics Technology and High Purity Materials, Russian Academy of Science, 6, Academician Ossipyan str., Chernogolovka, Moscow Region 142432 (Russian Federation); Polyakov, A. Y. [National University of Science and Technology MISiS, Leninskiy pr. 4, Moscow 119049 (Russian Federation); Lee, In-Hwan [School of Advanced Materials Engineering and Research Center of Advanced Materials Development, Chonbuk National University, Jeonju 561-756 (Korea, Republic of); Pearton, S. J. [University of Florida, Gainesville, Florida 32611 (United States)

    2015-03-30

    The movement of basal plane segments of dislocations in low-dislocation-density GaN films grown by epitaxial lateral overgrowth as a result of irradiation with the probing beam of a scanning electron microscope was detected by means of electron beam induced current. Only a small fraction of the basal plane dislocations was susceptible to such changes and the movement was limited to relatively short distances. The effect is explained by the radiation enhanced dislocation glide for dislocations pinned by two different types of pinning sites: a low-activation-energy site and a high-activation-energy site. Only dislocation segments pinned by the former sites can be moved by irradiation and only until they meet the latter pinning sites.

  14. Linneg Sca-1high CD49fhigh prostate cancer cells derived from the Hi-Myc mouse model are tumor-initiating cells with basal-epithelial characteristics and differentiation potential in vitro and in vivo.

    Science.gov (United States)

    Saha, Achinto; Blando, Jorge; Fernandez, Irina; Kiguchi, Kaoru; DiGiovanni, John

    2016-05-03

    A cell line was established from ventral prostate (VP) tumors of one-year-old Hi-Myc mice. These cells, called HMVP2 cells, are LinnegSca-1highCD49fhigh with high CD44 and CD29 expression and express CK14, Sca-1 and CD49f (but not CK8), suggesting basal-epithelial characteristics. Furthermore, HMVP2 cells form spheroids and both the cells and spheroids produce tumors in syngeneic mice. After four days of culture, HMVP2 spheroids underwent a gradual transition from LinnegSca-1highCD49fhigh expression to LinnegSca-1lowCD49flow while a subpopulation of the cells retained the original LinnegSca-1highCD49fhigh expression pattern. Additional cell subpopulations expressing Lin positive markers were also present suggesting further differentiation of HMVP2 spheroids. Two additional highly tumorigenic cell lines (HMVP2A1 and HMVP2A2) were isolated from HMVP2 cells after subsequent tumor formation in FVB/N mice. Concurrently, we also established cell lines from the VP of 6 months old Hi-Myc mice (named as HMVP1) and FVB/N mice (called NMVP) having less aggressive growth properties compared to the other three cell lines. AR expression was reduced in HMVP2 cells compared to NMVP and HMVP1 cells and almost absent in HMVP2A1 and HMVP2A2 cells. These cell lines will provide valuable tools for further mechanistic studies as well as preclinical studies to evaluate preventive and/or therapeutic agents for prostate cancer.

  15. Neural activity in the rat basal ganglia

    NARCIS (Netherlands)

    Zhao, Y.; Stegenga, J.; Heida, T.; Wezel, van R.J.A.

    2013-01-01

    Objectives: Pathological oscillations in the beta frequencies (8-30Hz) have been found in the local field potentials of Parkinson's disease (PD) patients and non-human primate models of PD1. In particular, these synchronizations appear in the subthalamic nucleus (STN), a common target for deep brain

  16. High Energy Activation Data Library (HEAD-2009)

    CERN Document Server

    Korovin, Yury A; Konobeyev, Alexander Yu; Stankovskiy, Alexey Yu; Mashnik, Stepan G

    2010-01-01

    A proton activation data library for 682 nuclides from 1-H to 210-Po in the energy range from 150 MeV up to 1 GeV was developed. To calculate proton activation data, the MCNPX 2.6.0 and CASCADE/INPE codes were chosen. Different intranuclear cascade, preequilibrium, and equilibrium nuclear reaction models and their combinations were used. The optimum calculation models have been chosen on the basis of statistical correlations for calculated and experimental proton data taken from the EXFOR library of experimental nuclear data. All the data are written in ENDF-6 format. The library is called HEPAD-2008 (High-Energy Proton Activation Data). A revision of IEAF-2005 neutron activation data library has been performed: A set of nuclides for which the cross-section data can be (and were) updated using more modern and improved models is specified, and the corresponding calculations have been made in the present work. The new version of the library is called IEAF-2009. The HEPAD-2008 and IEAF-2009 are merged to the fin...

  17. Marine ice sheet model performance depends on basal sliding physics and sub-shelf melting

    Science.gov (United States)

    Gladstone, Rupert Michael; Warner, Roland Charles; Galton-Fenzi, Benjamin Keith; Gagliardini, Olivier; Zwinger, Thomas; Greve, Ralf

    2017-01-01

    Computer models are necessary for understanding and predicting marine ice sheet behaviour. However, there is uncertainty over implementation of physical processes at the ice base, both for grounded and floating glacial ice. Here we implement several sliding relations in a marine ice sheet flow-line model accounting for all stress components and demonstrate that model resolution requirements are strongly dependent on both the choice of basal sliding relation and the spatial distribution of ice shelf basal melting.Sliding relations that reduce the magnitude of the step change in basal drag from grounded ice to floating ice (where basal drag is set to zero) show reduced dependence on resolution compared to a commonly used relation, in which basal drag is purely a power law function of basal ice velocity. Sliding relations in which basal drag goes smoothly to zero as the grounding line is approached from inland (due to a physically motivated incorporation of effective pressure at the bed) provide further reduction in resolution dependence.A similar issue is found with the imposition of basal melt under the floating part of the ice shelf: melt parameterisations that reduce the abruptness of change in basal melting from grounded ice (where basal melt is set to zero) to floating ice provide improved convergence with resolution compared to parameterisations in which high melt occurs adjacent to the grounding line.Thus physical processes, such as sub-glacial outflow (which could cause high melt near the grounding line), impact on capability to simulate marine ice sheets. If there exists an abrupt change across the grounding line in either basal drag or basal melting, then high resolution will be required to solve the problem. However, the plausible combination of a physical dependency of basal drag on effective pressure, and the possibility of low ice shelf basal melt rates next to the grounding line, may mean that some marine ice sheet systems can be reliably simulated at

  18. 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

    2015-01-01

    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 in

  19. Basal Cell Carcinoma in Young Patients

    Directory of Open Access Journals (Sweden)

    Uğur Horoz

    2017-03-01

    Full Text Available Basal cell carcinoma (BCC is the most common type of skin cancer and has a direct relationship with chronic sun exposure. Other risk factors include fair skin and eyes, freckling, family history, genetic disorders, immunosuppression, ionizing radiation, arsenic, and polyaromatic hydrocarbons. BCC usually progresses slowly. Lesions are usually seen over sun-exposed areas, which are most commonly on the face and neck. Local invasion may occur, but it rarely metastasizes. The incidence of BCC peaks in the seventh decade of life. BCC is an uncommon lesion during childhood, youth, and pregnancy. It has rarely been reported during childhood. BCC seen during childhood can be inherited with diseases such as xeroderma pigmentosum, albinism, Bazex syndrome, and basal cell nevus syndrome or after high-dose radiotherapy. In this study, we present the cases of a 14-year-old girl with BCC on the right popliteal region and a 23-year-old pregnant woman with BCC on the nasal tip. Both patients underwent total excision, and there were neither recurrence nor any complication during the follow-up

  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. Metacognitive Theory Applied: Strategic Reading Instruction in the Current Generation of Basal Readers.

    Science.gov (United States)

    Schmitt, Maribeth Cassidy; Hopkins, Carol J.

    1993-01-01

    Examines the content of eight basal reading series (published in 1989) to determine how and the extent to which lessons and activities that promote metacomprehension behaviors necessary for independent reading were included. Finds that basal authors made considerable efforts to incorporate activities and lessons that promote or foster strategic…

  2. Concrete with Highly Active Rice Husk Ash

    Institute of Scientific and Technical Information of China (English)

    FENG Qing-ge; LIN Qing-yu; YU Qi-jun; ZHAO San-ying; YANG Lu-feng; Shuichi Sugita

    2004-01-01

    The overall aim was to investigate the effect of highly active rice husk ash (RHA) produced by an industrial furnace on some properties of concrete. The strength, pore volume and pore distribution of concrete and the Ca(OH)2 content in concrete were investigated by JIS A 1108 (Method of test for compressive strength of concrete), a mercury instrument porosimeter, and the thermogravimetric analysis, respectively. The results show that,with RHA replacement of cement,the compressive strength of concrete is increased evidently;the average pore radius of concrete is greatly decreased, especially the portion of the pores greater than 20nm in radius is decreased while the amount of smaller pores is increased, and the more the RHA replacement, the less the amount of Ca(OH)2 in concrete. The latter two results are the main reasons for the strength enhancement of concrete.

  3. Dopaminergic parameters during social isolation in low- and high-active mice.

    Science.gov (United States)

    Rilke, O; Jähkel, M; Oehler, J

    1998-06-01

    Alterations induced by social isolation (1 day to 18 weeks) in low- and high-active mice (LAM and HAM) were studied in respect to locomotor activity, [3H]-spiperone binding in the striatum, striatal, and cortical dopamine metabolism, and presynaptic dopaminergic sensitivity to apomorphine (0.75 mg/kg; i.p.). Isolated HAM and LAM showed increased locomotor activity compared to group-housed mice after long-term isolation (6-18 weeks). Considering the studied dopaminergic parameters, it has been found that social isolation did not affect striatal D2 receptors, striatal and cortical dopamine metabolism, and apomorphine-mediated reduction of dopaminergic metabolism. The change of housing conditions was generally associated with an increase of cortical dopamine metabolism after 1 week. Activity type specific differences in group-housed LAM and HAM were found in the basal striatal dopamine metabolism and in the sensitivity of the nigrostriatal system to autoreceptor activation. The reduced striatal dopamine metabolism and the higher presynaptic sensitivity of HAM may be related to their high active running wheel behavior.

  4. The Basal Ganglia and Motor Control

    OpenAIRE

    Groenewegen, Henk J.

    2003-01-01

    This paper briefly reviews the functional anatomy of the basal ganglia and their relationships with the thalamocortical system. The basal ganglia, including the striatum, pallidum, subthalamic nucleus, and substantia nigra, are involved in a number of parallel, functionally segregated cortical-subcortical circuits. These circuits support a wide range of sensorimotor, cognitive and emotional-motivational brain functions. A main role of the basal ganglia is the learning and selection of the mos...

  5. Functional Neuroanatomy of the Basal Ganglia

    OpenAIRE

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

    2012-01-01

    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 amp...

  6. 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. Low-freq

  7. Visualization of Active Glucocerebrosidase in Rodent Brain with High Spatial Resolution following In Situ Labeling with Fluorescent Activity Based Probes.

    Directory of Open Access Journals (Sweden)

    Daniela Herrera Moro Chao

    Full Text Available Gaucher disease is characterized by lysosomal accumulation of glucosylceramide due to deficient activity of lysosomal glucocerebrosidase (GBA. In cells, glucosylceramide is also degraded outside lysosomes by the enzyme glucosylceramidase 2 (GBA2 of which inherited deficiency is associated with ataxias. The interest in GBA and glucosylceramide metabolism in the brain has grown following the notion that mutations in the GBA gene impose a risk factor for motor disorders such as α-synucleinopathies. We earlier developed a β-glucopyranosyl-configured cyclophellitol-epoxide type activity based probe (ABP allowing in vivo and in vitro visualization of active molecules of GBA with high spatial resolution. Labeling occurs through covalent linkage of the ABP to the catalytic nucleophile residue in the enzyme pocket. Here, we describe a method to visualize active GBA molecules in rat brain slices using in vivo labeling. Brain areas related to motor control, like the basal ganglia and motor related structures in the brainstem, show a high content of active GBA. We also developed a β-glucopyranosyl cyclophellitol-aziridine ABP allowing in situ labeling of GBA2. Labeled GBA2 in brain areas can be identified and quantified upon gel electrophoresis. The distribution of active GBA2 markedly differs from that of GBA, being highest in the cerebellar cortex. The histological findings with ABP labeling were confirmed by biochemical analysis of isolated brain areas. In conclusion, ABPs offer sensitive tools to visualize active GBA and to study the distribution of GBA2 in the brain and thus may find application to establish the role of these enzymes in neurodegenerative disease conditions such as α-synucleinopathies and cerebellar ataxia.

  8. Kinome expression profiling and prognosis of basal breast cancers

    Directory of Open Access Journals (Sweden)

    Jacquemier Jocelyne

    2011-07-01

    Full Text Available Abstract Background Basal breast cancers (BCs represent ~15% of BCs. Although overall poor, prognosis is heterogeneous. Identification of good- versus poor-prognosis patients is difficult or impossible using the standard histoclinical features and the recently defined prognostic gene expression signatures (GES. Kinases are often activated or overexpressed in cancers, and constitute targets for successful therapies. We sought to define a prognostic model of basal BCs based on kinome expression profiling. Methods DNA microarray-based gene expression and histoclinical data of 2515 early BCs from thirteen datasets were collected. We searched for a kinome-based GES associated with disease-free survival (DFS in basal BCs of the learning set using a metagene-based approach. The signature was then tested in basal tumors of the independent validation set. Results A total of 591 samples were basal. We identified a 28-kinase metagene associated with DFS in the learning set (N = 73. This metagene was associated with immune response and particularly cytotoxic T-cell response. On multivariate analysis, a metagene-based predictor outperformed the classical prognostic factors, both in the learning and the validation (N = 518 sets, independently of the lymphocyte infiltrate. In the validation set, patients whose tumors overexpressed the metagene had a 78% 5-year DFS versus 54% for other patients (p = 1.62E-4, log-rank test. Conclusions Based on kinome expression, we identified a predictor that separated basal BCs into two subgroups of different prognosis. Tumors associated with higher activation of cytotoxic tumor-infiltrative lymphocytes harbored a better prognosis. Such classification should help tailor the treatment and develop new therapies based on immune response manipulation.

  9. 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

  10. Phylogeny of basal iguanodonts (Dinosauria: Ornithischia: an update.

    Directory of Open Access Journals (Sweden)

    Andrew T McDonald

    Full Text Available The precise phylogenetic relationships of many non-hadrosaurid members of Iguanodontia, i.e., basal iguanodonts, have been unclear. Therefore, to investigate the global phylogeny of basal iguanodonts a comprehensive data matrix was assembled, including nearly every valid taxon of basal iguanodont. The matrix was analyzed in the program TNT, and the maximum agreement subtree of the resulting most parsimonious trees was then calculated in PAUP. Ordering certain multistate characters and omitting taxa through safe taxonomic reduction did not markedly improve resolution. The results provide some new information on the phylogeny of basal iguanodonts, pertaining especially to obscure or recently described taxa, and support some recent taxonomic revisions, such as the splitting of traditional "Camptosaurus" and "Iguanodon". The maximum agreement subtree also shows a close relationship between the Asian Probactrosaurus gobiensis and the North American Eolambia, supporting the previous hypothesis of faunal interchange between Asia and North America in the early Late Cretaceous. Nevertheless, the phylogenetic relationships of many basal iguanodonts remain ambiguous due to the high number of taxa removed from the maximum agreement subtree and poor resolution of consensus trees.

  11. Phylogeny of basal iguanodonts (Dinosauria: Ornithischia): an update.

    Science.gov (United States)

    McDonald, Andrew T

    2012-01-01

    The precise phylogenetic relationships of many non-hadrosaurid members of Iguanodontia, i.e., basal iguanodonts, have been unclear. Therefore, to investigate the global phylogeny of basal iguanodonts a comprehensive data matrix was assembled, including nearly every valid taxon of basal iguanodont. The matrix was analyzed in the program TNT, and the maximum agreement subtree of the resulting most parsimonious trees was then calculated in PAUP. Ordering certain multistate characters and omitting taxa through safe taxonomic reduction did not markedly improve resolution. The results provide some new information on the phylogeny of basal iguanodonts, pertaining especially to obscure or recently described taxa, and support some recent taxonomic revisions, such as the splitting of traditional "Camptosaurus" and "Iguanodon". The maximum agreement subtree also shows a close relationship between the Asian Probactrosaurus gobiensis and the North American Eolambia, supporting the previous hypothesis of faunal interchange between Asia and North America in the early Late Cretaceous. Nevertheless, the phylogenetic relationships of many basal iguanodonts remain ambiguous due to the high number of taxa removed from the maximum agreement subtree and poor resolution of consensus trees.

  12. Mephedrone alters basal ganglia and limbic neurotensin systems.

    Science.gov (United States)

    German, Christopher L; Hoonakker, Amanda H; Fleckenstein, Annette E; Hanson, Glen R

    2014-08-01

    Mephedrone (4-methylmethcathinone) is a synthetic cathinone designer drug that alters pre-synaptic dopamine (DA) activity like many psychostimulants. However, little is known about the post-synaptic dopaminergic impacts of mephedrone. The neuropeptide neurotensin (NT) provides inhibitory feedback for basal ganglia and limbic DA pathways, and post-synaptic D1 -like and D2 -like receptor activity affects NT tissue levels. This study evaluated how mephedrone alters basal ganglia and limbic system NT content and the role of NT receptor activation in drug consumption behavior. Four 25 mg/kg injections of mephedrone increased NT content in basal ganglia (striatum, substantia nigra and globus pallidus) and the limbic regions (nucleus accumbens core), while a lower dosage (5 mg/kg/injection) only increased striatal NT content. Mephedrone-induced increases in basal ganglia NT levels were mediated by D1 -like receptors in the striatum and the substantia nigra by both D1 -like and D2 -like receptors in the globus pallidus. Mephedrone increased substance P content, another neuropeptide, in the globus pallidus, but not in the dorsal striatum or substantia nigra. Finally, the NT receptor agonist PD149163 blocked mephedrone self-administration, suggesting reduced NT release, as indicated by increased tissue levels, likely contributing to patterns of mephedrone consumption.

  13. 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

    NARCIS (Netherlands)

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

    2015-01-01

    BACKGROUND: 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-

  14. Basal cell carcinomas in elderly patients treated by cryotherapy

    Directory of Open Access Journals (Sweden)

    Chiriac A

    2013-03-01

    Full Text Available Anca Chiriac,1 Doina Mihaila,2 Liliana Foia,3, Caius Solovan4 1Department of Dermatology, Nicolina Medical Center, 2Department of Pathology, St Maria Children's Hospital, 3Surgical Department, Grigore T Popa University of Medicine and Pharmacy, Iaşi, Romania; 4Victor Babe University of Medicine, Timişoara, Romania Abstract: Basal cell carcinoma is a malignant skin tumor with high incidence in our country, especially in rural areas, on sun-exposed skin (particularly on the face in elderly patients. We present three cases of basal cell carcinoma with good results with cryotherapy. This report aims to outline and to prove that in some difficult situations, a simple, inexpensive, easy-to-perform procedure with no contraindications and with minimal side effects (erythema, mild pain can be applied and resolve such cases. Keywords: basal cell carcinoma, cryotherapy

  15. 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.

  16. High-Throughput Analysis of Enzyme Activities

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Guoxin [Iowa State Univ., Ames, IA (United States)

    2007-01-01

    High-throughput screening (HTS) techniques have been applied to many research fields nowadays. Robot microarray printing technique and automation microtiter handling technique allows HTS performing in both heterogeneous and homogeneous formats, with minimal sample required for each assay element. In this dissertation, new HTS techniques for enzyme activity analysis were developed. First, patterns of immobilized enzyme on nylon screen were detected by multiplexed capillary system. The imaging resolution is limited by the outer diameter of the capillaries. In order to get finer images, capillaries with smaller outer diameters can be used to form the imaging probe. Application of capillary electrophoresis allows separation of the product from the substrate in the reaction mixture, so that the product doesn't have to have different optical properties with the substrate. UV absorption detection allows almost universal detection for organic molecules. Thus, no modifications of either the substrate or the product molecules are necessary. This technique has the potential to be used in screening of local distribution variations of specific bio-molecules in a tissue or in screening of multiple immobilized catalysts. Another high-throughput screening technique is developed by directly monitoring the light intensity of the immobilized-catalyst surface using a scientific charge-coupled device (CCD). Briefly, the surface of enzyme microarray is focused onto a scientific CCD using an objective lens. By carefully choosing the detection wavelength, generation of product on an enzyme spot can be seen by the CCD. Analyzing the light intensity change over time on an enzyme spot can give information of reaction rate. The same microarray can be used for many times. Thus, high-throughput kinetic studies of hundreds of catalytic reactions are made possible. At last, we studied the fluorescence emission spectra of ADP and obtained the detection limits for ADP under three different

  17. Metabolic Activity of Bacteria at High Pressure

    Science.gov (United States)

    Picard, A.; Daniel, I.; Oger, P.

    2008-12-01

    Over the last 20 years, there has been increasing evidence for the presence of a large number of microbes in the oceanic subsurface. Such a habitat has a very low energy input because it is deprived of light. A few meters below the sediment surface, conditions are already anoxic in most cases, sulfate reduction and/or methanogenesis becoming thus the primary respiratory reactions of organic matter. Neither the fate of methanogenesis, nor the fate of Dissimilatory Metal-Reduction (DMR) has been investigated so far as a function of pressure. For this reason, we measured experimentally the pressure limits of microbial anaerobic energetic metabolism. In practice, we measured in situ the kinetics of selenite respiration by the bacterial model Shewanella oneidensis MR-1 under high hydrostatic pressure (HHP) between 0 and 150 MPa at 30°C. MR-1 stationary-phase cells were used in Luria-Bertani (LB) medium amended with lactate as an additional electron donor and sodium selenite as an electron acceptor. In situ measurements were performed by X- ray Absorption Near-Edge Structure (XANES) spectroscopy in both a diamond-anvil cell and an autoclave. A red precipitate of amorphous Se(0) was virtually observed at any pressure to 150 MPa. A progressive reduction of selenite Se(IV) into selenium Se(0) was also observed in the evolution of XANES spectra with time. All kinetics between 0.1 and 150 MPa can be adjusted to a first order kinetic law. MR-1 respires all available selenite up to 60 MPa. Above 60 MPa, the respiration yield decreases linearly as a function of pressure and reaches 0 at 155 ±5 MPa. This indicates that selenite respiration by Shewanella oneidensis MR-1 stops at about 155 MPa, whereas its growth is arrested at 50 MPa. Hence, the present results show that the respiration of selenium by the strain MR-1 occurs efficiently up to 60 MPa and 30°C, i.e. from the surface of a continental sediment to an equivalent depth of about 2 km, or beneath a 5-km water column and

  18. Diabetes reduces basal retinal insulin receptor signaling: reversal with systemic and local insulin.

    Science.gov (United States)

    Reiter, Chad E N; Wu, Xiaohua; Sandirasegarane, Lakshman; Nakamura, Makoto; Gilbert, Kirk A; Singh, Ravi S J; Fort, Patrice E; Antonetti, David A; Gardner, Thomas W

    2006-04-01

    Diabetic retinopathy is characterized by early onset of neuronal cell death. We previously showed that insulin mediates a prosurvival pathway in retinal neurons and that normal retina expresses a highly active basal insulin receptor/Akt signaling pathway that is stable throughout feeding and fasting. Using the streptozotocin-induced diabetic rat model, we tested the hypothesis that diabetes diminishes basal retinal insulin receptor signaling concomitantly with increased diabetes-induced retinal apoptosis. The expression, phosphorylation status, and/or kinase activity of the insulin receptor and downstream signaling proteins were investigated in retinas of age-matched control, diabetic, and insulin-treated diabetic rats. Four weeks of diabetes reduced basal insulin receptor kinase, insulin receptor substrate (IRS)-1/2-associated phosphatidylinositol 3-kinase, and Akt kinase activity without altering insulin receptor or IRS-1/2 expression or tyrosine phosphorylation. After 12 weeks of diabetes, constitutive insulin receptor autophosphorylation and IRS-2 expression were reduced, without changes in p42/p44 mitogen-activated protein kinase or IRS-1. Sustained systemic insulin treatment of diabetic rats prevented loss of insulin receptor and Akt kinase activity, and acute intravitreal insulin administration restored insulin receptor kinase activity. Insulin treatment restored insulin receptor-beta autophosphorylation in rat retinas maintained ex vivo, demonstrating functional receptors and suggesting loss of ligand as a cause for reduced retinal insulin receptor/Akt pathway activity. These results demonstrate that diabetes progressively impairs the constitutive retinal insulin receptor signaling pathway through Akt and suggests that loss of this survival pathway may contribute to the initial stages of diabetic retinopathy.

  19. Early recognition of basal cell naevus syndrome

    NARCIS (Netherlands)

    Veenstra-Knol, HE; Scheewe, JH; van der Vlist, GJ; van Doorn, ME; Ausems, MGEM

    2005-01-01

    The basal cell naevus syndrome is an autosomal dominant syndrome characterised by major manifestations such as basal cell carcinomas, jaw cysts, palmar or plantar pits, and intracranial calcifications. Early recognition is important in order to reduce morbidity due to cutaneous and cerebral malignan

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

    DEFF Research Database (Denmark)

    Su, Ying; Subedee, Ashim; Bloushtain-Qimron, Noga;

    2015-01-01

    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......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...... 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...

  1. Cold basal conditions during surges control flow of fringing Arctic ice caps in Greenland

    Science.gov (United States)

    Cook, Samuel; Christoffersen, Poul; Todd, Joe; Palmer, Steven

    2017-04-01

    Fringing ice caps separated from larger ice sheets are rarely studied, yet they are an important part of earth's cryosphere, which has become the largest source of global sea-level rise. Understanding marginal ice caps is crucial for being able to predict sea-level change as they are responsible for up to 20% of Greenland's mass loss for 2003-2008. Studies of fringing ice caps can furthermore provide useful insights into processes operating on glaciers that surge. Surging has been the focus of much recent glaciological work, especially with reference to thermal evolution of polythermal glaciers in High Mountain Asia and the High Arctic. This has shown that the classic divide between hydrologically-controlled surges ('hard-bed') in Alaska and thermally-regulated ('soft-bed') surges elsewhere is less stark than previously assumed. Studying marginal ice caps can therefore be valuable in several ways. The largest fringing ice cap in Greenland is Flade Isblink. Previous work has established that this ice cap is showing a range of dynamic behaviour, including subglacial lake drainage and varied patterns of mass-balance change. In particular, a substantial surge, assumed to be caused by a version of the thermally-regulated mechanism, occurred between 1996 and 2000, making the ice cap a useful case study for investigating this process. Here we investigate the surge on Flade Isblink using the open-source, Full-Stokes model Elmer/Ice to invert for basal conditions and englacial temperatures using the adjoint method. We specifically study steady-state conditions representative of the active surge phase in 2000, and the subsequent quiescent phase, using patterns of surface velocity observed in 2000, 2005, 2008 and 2015. Under constant geometry, temperature and geothermal heat, it is shown that surging increases basal freezing rates by over 60% across an area that is twice as large as the area over which the bed freezes in the quiescent phase. The process responsible for this

  2. Multiple drug resistance-associated protein (MRP4) exports prostaglandin E2 (PGE2) and contributes to metastasis in basal/triple negative breast cancer.

    Science.gov (United States)

    Kochel, Tyler J; Reader, Jocelyn C; Ma, Xinrong; Kundu, Namita; Fulton, Amy M

    2017-01-24

    Cyclooxygenase-2 (COX-2) and its primary enzymatic product, prostaglandin E2 (PGE2), are associated with a poor prognosis in breast cancer. In order to elucidate the factors contributing to intratumoral PGE2 levels, we evaluated the expression of COX-2/PGE2 pathway members MRP4, the prostaglandin transporter PGT, 15-PGDH (PGE2 metabolism), the prostaglandin E receptor EP4, COX-1, and COX-2 in normal, luminal, and basal breast cancer cell lines. The pattern of protein expression varied by cell line reflecting breast cancer heterogeneity. Overall, basal cell lines expressed higher COX-2, higher MRP4, lower PGT, and lower 15-PGDH than luminal cell lines resulting in higher PGE2 in the extracellular environment. Genetic or pharmacologic suppression of MRP4 expression or activity in basal cell lines led to less extracellular PGE2. The key finding is that xenografts derived from a basal breast cancer cell line with stably suppressed MRP4 expression showed a marked decrease in spontaneous metastasis compared to cells with unaltered MRP4 expression. Growth properties of primary tumors were not altered by MRP4 manipulation. In addition to the well-established role of high COX-2 in promoting metastasis, these data identify an additional mechanism to achieve high PGE2 in the tumor microenvironment; high MRP4, low PGT, and low 15-PGDH. MRP4 should be examined further as a potential therapeutic target in basal breast cancer.

  3. 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.

  4. Neglected giant scalp Basal cell carcinoma

    DEFF Research Database (Denmark)

    Larsen, Anne Kristine; El-Charnoubi, Waseem-Asim Ghulam; Gehl, Julie;

    2014-01-01

    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...

  5. Thermodynamic Significance of Human Basal Metabolism

    Institute of Scientific and Technical Information of China (English)

    WangCuncheng

    1993-01-01

    The human basal state,a non-equilibrium steady state,is analysed in this paper in the light of the First and Second Laws of Thermodynamics whereby the thermodynamic significance of the basal metabolic rate and its distinction to the dissipation function and exergy loss are identified.The analysis demonstrates the correct expression of the effects of the blood flow on the heat balance in a human-body bio-heat model and the relationship between the basal metabolic rate and the blood perfusion.

  6. 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

    Full Text Available BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS/SIGNIFICANCE: 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.

  7. An Integrated Assessment of Basal Scattering and Topographic Roughness Information Derived from Greenland Radar-Sounding Data

    Science.gov (United States)

    Gillet-chaulet, F.; Jordan, T.; Cooper, M.; Bamber, J. L.; Schroeder, D. M.; Williams, C.; Paden, J. D.; Siegert, M. J.; Huybrechts, P.; Gagliardini, O.; Price, S. F.

    2016-12-01

    Quantifying the basal roughness of ice sheets is important for understanding and constraining the role of basal traction on ice dynamics. Numerical model simulations demonstrate high sensitivity to the parametrisation of the lower boundary condition, which is governed by both basal roughness and the thermal state of the bed. In terms of ice dynamics history, basal roughness can reveal aspects of past behaviour as well as provide insight towards more recent flow distribution of marine sediments. Basal roughness information, defined here in general terms as the irregularity of the basal interface relative to a reference surface, can be obtained from radar-sounding data in two physically different ways. Firstly, via the statistical properties of along-track topography (e.g. from spectral analysis); and secondly via the electromagnetic scattering properties of the radar pulse (e.g. by quantifying the spread of the distribution of scattered energy). In general, the basal roughness of the Greenland Ice Sheet has been little studied, and the vast increase in recent Operation Ice Bridge radar-sounding data presents an opportunity for comprehensive, quantitative ice-sheet-wide analysis. Here we present a synthesis of basal scattering and topographic based roughness information for the Greenland Ice Sheet, along with a comparison to present day numerical model output including ice velocity, basal traction, and basal temperature. One central topic which we address is the scale dependence of basal roughness information that is inferred from both analysis methods, and the relationship with basal sliding physics. Consideration of scale is important since basal sliding is primarily controlled by higher frequency roughness. The other topic that we consider is identifying whether there are any defined and unambiguous roughness characteristics in regions where there is suspected to be a thawed basal interface. An overall goal of this work is to integrate basal roughness information

  8. Seismic signals associated with basal processes of the Greenland Ice Sheet

    Science.gov (United States)

    Röösli, Claudia; Walter, Fabian; Kisslin, Edi; Helmstetter, Agnes; Lüthi, Martin

    2014-05-01

    Understanding ice sheet and glacier dynamics is crucial for modeling of ice mass balance and resulting sea level changes. Ice dynamics is strongly influenced by surface melt water accumulating at the glacier base and its effect on basal sliding. The relationship between surface melt and ice flow depends on hydraulic processes in the subglacial drainage system. However, both subglacial and englacial drainage systems are inherently difficult to investigate due to their remoteness, and basal processes to date remain poorly understood. Borrowing concepts from volcano studies, recent glacier studies are employing passive seismology as a supplement to traditional glaciological techniques. When monitoring the seismic activity of a glacier or an ice sheet, several different types of so-called 'icequakes' and some times even 'tremor' may be detected in the seismic records that is dominated by the large number of surficial icequakes. Deep icequakes may provide information about englacial water flow and basal motion in response to hydraulic events over a region whose size is only limited by seismic background noise and the aperture of the monitoring network. Here, we present results from a passive seismic deployment on western Greenland's ablation zone during summer 2011. The high-density seismometer network consisted of 17 three-component stations installed at the ice surface or in boreholes. We recorded a large variety of seismic signals, including thousands of near-surface crevasse events as well as dislocation events deep within the ice sheet and near its bed. We discuss these 'deep icequakes' in view of hydraulic processes and basal motion. Furthermore, the seismic deployment was part of larger field campaign including a deep drilling project and glaciological surface observations. This provides the unique opportunity to interpret the seismic monitoring results within the variety of observations including subglacial water pressures and other borehole measurements.

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

    Science.gov (United States)

    O'Donnell, Emily C.; Wadham, Jemma L.; Lis, Grzegorz P.; Tranter, Martyn; Pickard, Amy E.; Stibal, Marek; Dewsbury, Paul; Fitzsimons, Sean

    2016-07-01

    Determining the concentration and composition of dissolved organic carbon (DOC) in glacial ecosystems is important for assessments of in situ microbial activity and contributions to wider biogeochemical cycles. Nonetheless, there is limited knowledge of the abundance and character of DOC in basal ice and the subglacial environment and a lack of quantitative data on low-molecular-weight (LMW) DOC components, which are believed to be highly bioavailable to microorganisms. We investigated the abundance and composition of DOC in basal ice via a molecular-level DOC analysis. Spectrofluorometry and a novel ion chromatographic method, which has been little utilized 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 type of overridden material (i.e. the pre-entrainment sedimentary type such as lacustrine material or palaeosols). Basal ice from Joyce Glacier (Antarctica) was unique in that 98 % of the LMW-DOC was derived from the extremely diverse free amino acid (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 palaeosols 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

  10. Body composition and basal metabolic rate in Hidradenitis Suppurativa

    DEFF Research Database (Denmark)

    Miller, I M; Rytgaard, Helene Charlotte; Mogensen, U B

    2016-01-01

    BACKGROUND: Several studies have suggested an association between Hidradenitis Suppurativa (HS) and obesity. Obesity is often expressed as Body Mass Index (BMI). However, BMI lacks information on body composition. General obesity is a predictor of health status and cardiovascular risk, but body.......70-105.56) (P Hidradenitis Suppurativa is associated with a high fat percentage, high visceral fat, and low muscle percentage adding to the morbidity of HS. The higher predicted estimate of basal metabolic rate (BMR) in HS patients may reflect...

  11. Apico-basal polarity complex and cancer

    Indian Academy of Sciences (India)

    Mohammed Khursheed; Murali Dharan Bashyam

    2014-03-01

    Apico-basal polarity is a cardinal molecular feature of adult eukaryotic epithelial cells and appears to be involved in several key cellular processes including polarized cell migration and maintenance of tissue architecture. Epithelial cell polarity is maintained by three well-conserved polarity complexes, namely, PAR, Crumbs and SCRIB. The location and interaction between the components of these complexes defines distinct structural domains of epithelial cells. Establishment and maintenance of apico-basal polarity is regulated through various conserved cell signalling pathways including TGF, Integrin and WNT signalling. 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 overview of the apico-basal polarity complexes and their regulation, their role in cell migration, and finally their involvement in carcinogenesis.

  12. Insulin pumps: Beyond basal-bolus

    National Research Council Canada - National Science Library

    Millstein, Richard; Becerra, Nancy Mora; Shubrook, Jay H

    2015-01-01

    Insulin pumps are a major advance in diabetes management, making insulin dosing easier and more accurate and providing great flexibility, safety, and efficacy for people who need basal-bolus insulin therapy...

  13. Highly active thermally stable nanoporous gold catalyst

    Science.gov (United States)

    Biener, Juergen; Wittstock, Arne; Biener, Monika M.; Bagge-Hansen, Michael; Baeumer, Marcus; Wichmann, Andre; Neuman, Bjoern

    2016-12-20

    In one embodiment, a system includes a nanoporous gold structure and a plurality of oxide particles deposited on the nanoporous gold structure; the oxide particles are characterized by a crystalline phase. In another embodiment, a method includes depositing oxide nanoparticles on a nanoporous gold support to form an active structure and functionalizing the deposited oxide nanoparticles.

  14. Highly active thermally stable nanoporous gold catalyst

    Energy Technology Data Exchange (ETDEWEB)

    Biener, Juergen; Wittstock, Arne; Biener, Monika M.; Bagge-Hansen, Michael; Baeumer, Marcus; Wichmann, Andre; Neuman, Bjoern

    2016-12-20

    In one embodiment, a system includes a nanoporous gold structure and a plurality of oxide particles deposited on the nanoporous gold structure; the oxide particles are characterized by a crystalline phase. In another embodiment, a method includes depositing oxide nanoparticles on a nanoporous gold support to form an active structure and functionalizing the deposited oxide nanoparticles.

  15. Pathway-focused proteomic signatures in HER2-overexpressing breast cancer with a basal-like phenotype: new insights into de novo resistance to trastuzumab (Herceptin).

    Science.gov (United States)

    Oliveras-Ferraros, Cristina; Vazquez-Martin, Alejandro; Martin-Castilló, Begoña; Pérez-Martínez, Maria Carmen; Cufí, Silvia; Del Barco, Sonia; Bernado, Luis; Brunet, Joan; López-Bonet, Eugeni; Menendez, Javíer A

    2010-09-01

    Pioneering clinical studies in de novo refractoriness to the anti-HER2 monoclonal antibody trastuzumab have suggested that HER2 gene-amplification can take place also in a basal-like molecular background to generate basal/HER2+ tumors intrinsically resistant to trastuzumab. Here, we first investigated the unique histogenesis of the basal/HER2+ phenotype in breast carcinomas. The presence of basal CK5/CK6 cytokeratin expression in HER2+ tumors revealed a significant overlap in the histological features of HER2+/CK5/6+ and basal-like breast carcinomas. Basal/HER2+ tumors were typically poorly differentiated, high-grade invasive ductal carcinomas with large geographic necrosis, pushing margins of invasion, syncytial arrangement of tumor cells, ribbon- or festoon-like architecture, squamous metaplasia, stromal lymphocytic infiltrates, high mitotic index and strong p53 positivity. Secondly, we performed low-scale proteomic approaches in JIMT-1 cells, a unique model of HER2-gene amplified trastuzumab-resistant breast carcinoma with a basal-like phenotype, to develop biomarker signatures that may differentiate trastuzumab-responsive from non-responsive tumors. When applying antibody-based array technology to the extracellular milieu of trastuzumab-refractory JIMT-1 and trastuzumab-sensitive SKBR3 cell cultures, JIMT-1 cells were found to secrete higher amounts of several growth factors including amphiregulin, EGF, IGFBP-6, PDGF-AA, neurotrophins, TGFbeta and VEGF. Semi-quantitative signaling node multi-target sandwich ELISAs revealed that JIMT-1 cells drastically overactivate RelA, the prosurvival subunit of NF-kappaB as compared to trastuzumab-sensitive luminal/HER2+ SKBR3 cells. When simultaneously assessing the activation status of 42 receptor tyrosine kinases (RTK) using a human phospho-RTK array, JIMT-1 cells were found to constitutively display hyperactivation of the insulin-like growth factor-I receptor (IGF-1R). High-content immunofluorescence imaging revealed

  16. Biomarkers for Basal-like Breast Cancer

    OpenAIRE

    Choo, Jennifer R.; Torsten O. Nielsen

    2010-01-01

    Initially recognized through microarray-based gene expression profiling, basal-like breast cancer, for which we lack effective targeted therapies, is an aggressive form of carcinoma with a predilection for younger women. With some success, immunohistochemical studies have attempted to reproduce the expression profile classification of breast cancer through identification of subtype-specific biomarkers. This review aims to present an in depth summary and analysis of the current status of basal...

  17. Basal Cell Carcinoma Developing from Trichoepithelioma: Review of Three Cases

    Science.gov (United States)

    Satyanarayana, M. Ananta; Aryasomayajula, Sirish; Krishna, B.A. Rama

    2016-01-01

    Trichoepitheliomas (TE) are benign tumours but occasionally can undergo transformation to malignant neoplasms more commonly as Basal Cell Carcinoma (BCC). The correct diagnosis between these tumours is very important because basal cell carcinoma is locally aggressive neoplasm and requires total surgical excision with wide healthy margins while trichoepithelioma needs simple excision. We describe three patients who developed basal cell carcinoma with facial trichoepitheliomas. The only clinical feature that distinguished the carcinomas from the trichoepitheliomas was their larger size, in all three patients, one patient with recurrent, hyper pigmented swelling with surface ulceration and in another patient there are multiple trichoepitheliomas, and other family members are also affected. The history, clinical features and histopathological findings were suggestive of the evolution of basal cell carcinoma directly from trichoepithelioma in our first two cases, but in the third case TE and BCC were separate lesions on face and we are uncertain about whether the BCC developed independently or by transformation from a trichoepithelioma. Based on our clinicopathological observations in the three patients and reports in the recent literature, BCC with follicular differentiation and trichoepithelioma are considered to be highly related. PMID:27134936

  18. 成人自发性基底节区脑出血患者日常生活活动能力的影响因素%Factors Affecting Activities of Daily Living in Patients with Spontaneous Basal Ganglia Hemorrhage

    Institute of Scientific and Technical Information of China (English)

    张志竖; 邹耀兵; 肖静; 江思德; 潘成德; 饶富兰; 张建新; 唐明山

    2011-01-01

    Objective To investigate the factors affecting activities of daily life (ADD in patients with first basal ganglia hemorrhage, and to formulate intervention strategies for improving the capability of ADL. Methods A prospective study was conducted on 97 patients with the first spontaneous intracerebral hemorrhage who survived with no surgical treatment. Demographic risk factors for stroke were examined and National Institute of Health stroke scale (NIHSS) and Glasgow coma score (GCS) were recorded on the day of admission. White blood cell(WBC) count and plasma glucose (PG) were measured on the second day of hospitalization. NIHSS score and Barthel index (BI) were recorded 3 weeks after onset. Occurrences of urinary tract and lung infection were determined after discharge from hospital. BI was recorded by clinic or telephone follow-up 3 months after onset. Results The amount of bleeding,initial PG levels, WBC count and initial NIHSS score were independently associated with BI at 3 weeks and 3 months after spontaneous intracerebral hemorrhage. Furthermore, urinary tract infection and the history of ischemic stroke were associated with BI at 3 months after intracerebral hemorrhage. Conclusion Positive measures should be taken to control risk factors so as to improve the capability of ADL in patients with spontaneous intracerebral hemorrhage.%目的 探讨未行手术治疗的成人首发基底节区脑出血患者日常生活活动能力的影响因素,以期早期制定干预措施,提高患者日常生活活动能力.方法 采用前瞻性队列研究连续收集成人首发基底节区脑出血未行手术治疗且存活的患者97例.入院当天记录人口基线资料,进行卒中危险因素调查,行美国国立卫生研究所脑卒中评分(national institute of health stroke scale,NIHSS)和格拉斯哥昏迷评分(GCS);入院次日清晨行白细胞计数、空腹血糖等多项实验室指标的测定;发病3周行NIHSS评分及Barthel指数(Barthelindex

  19. Enhanced hepatic insulin signaling in the livers of high altitude native rats under basal conditions and in the livers of low altitude native rats under insulin stimulation: a mechanistic study.

    Science.gov (United States)

    Al Dera, Hussain; Eleawa, Samy M; Al-Hashem, Fahaid H; Mahzari, Moeber M; Hoja, Ibrahim; Al Khateeb, Mahmoud

    2017-07-01

    This study was designed to investigate the role of the liver in lowering fasting blood glucose levels (FBG) in rats native to high (HA) and low altitude (LA) areas. As compared with LA natives, besides the improved insulin and glucose tolerance, HA native rats had lower FBG, at least mediated by inhibition of hepatic gluconeogenesis and activation of glycogen synthesis. An effect that is mediated by the enhancement of hepatic insulin signaling mediated by the decreased phosphorylation of TSC induced inhibition of mTOR function. Such effect was independent of activation of AMPK nor stabilization of HIF1α, but most probably due to oxidative stress induced REDD1 expression. However, under insulin stimulation, and in spite of the less activated mTOR function in HA native rats, LA native rats had higher glycogen content and reduced levels of gluconeogenic enzymes with a more enhanced insulin signaling, mainly due to higher levels of p-IRS1 (tyr612).

  20. How Basal Ganglia Outputs Generate Behavior

    Directory of Open Access Journals (Sweden)

    Henry H. Yin

    2014-01-01

    Full Text Available The basal ganglia (BG are a collection of subcortical nuclei critical for voluntary behavior. According to the standard model, the output projections from the BG tonically inhibit downstream motor centers and prevent behavior. A pause in the BG output opens the gate for behavior, allowing the initiation of actions. Hypokinetic neurological symptoms, such as inability to initiate actions in Parkinson’s disease, are explained by excessively high firing rates of the BG output neurons. This model, widely taught in textbooks, is contradicted by recent electrophysiological results, which are reviewed here. In addition, I also introduce a new model, based on the insight that behavior is a product of closed loop negative feedback control using internal reference signals rather than sensorimotor transformations. The nervous system is shown to be a functional hierarchy comprising independent controllers occupying different levels, each level controlling specific variables derived from its perceptual inputs. The BG represent the level of transition control in this hierarchy, sending reference signals specifying the succession of body orientations and configurations. This new model not only explains the major symptoms in movement disorders but also generates a number of testable predictions.

  1. Molecular and functional expression of high conductance Ca 2+ activated K+ channels in the eel intestinal epithelium

    DEFF Research Database (Denmark)

    Lionetto, Maria G; Rizzello, Antonia; Giordano, Maria E;

    2008-01-01

    Several types of K(+) channels have been identified in epithelial cells. Among them high conductance Ca(2+)-activated K(+) channels (BK channels) are of relevant importance for their involvement in regulatory volume decrease (RVD) response following hypotonic stress. The aim of the present work...... and morphometric analysis on the intact tissue. BK(Ca) channels appeared to be localized along all the plasma membrane of the enterocytes; the apical part of the villi showed the most intense immunostaining. These channels were silent in basal condition, but were activated on both membranes (apical and basolateral......) by increasing intracellular Ca(2+) concentration with the Ca(2+) ionophore ionomycin (1 microM). BK(Ca) channels were also activated on both membranes by hypotonic swelling of the epithelium and their inhibition by 100 nM iberiotoxin (specific BK(Ca) inhibitor) abolished the Regulatory Volume Decrease (RVD...

  2. Stem cell and neurogenic gene-expression profiles link prostate basal cells to aggressive prostate cancer.

    Science.gov (United States)

    Zhang, Dingxiao; Park, Daechan; Zhong, Yi; Lu, Yue; Rycaj, Kiera; Gong, Shuai; Chen, Xin; Liu, Xin; Chao, Hsueh-Ping; Whitney, Pamela; Calhoun-Davis, Tammy; Takata, Yoko; Shen, Jianjun; Iyer, Vishwanath R; Tang, Dean G

    2016-02-29

    The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. Here we describe a genome-wide transcriptome analysis of human benign prostatic basal and luminal epithelial populations using deep RNA sequencing. Through molecular and biological characterizations, we show that the differential gene-expression profiles account for their distinct functional properties. Strikingly, basal cells preferentially express gene categories associated with stem cells, neurogenesis and ribosomal RNA (rRNA) biogenesis. Consistent with this profile, basal cells functionally exhibit intrinsic stem-like and neurogenic properties with enhanced rRNA transcription activity. Of clinical relevance, the basal cell gene-expression profile is enriched in advanced, anaplastic, castration-resistant and metastatic prostate cancers. Therefore, we link the cell-type-specific gene signatures to aggressive subtypes of prostate cancer and identify gene signatures associated with adverse clinical features.

  3. Basal ganglia outputs map instantaneous position coordinates during behavior.

    Science.gov (United States)

    Barter, Joseph W; Li, Suellen; Sukharnikova, Tatyana; Rossi, Mark A; Bartholomew, Ryan A; Yin, Henry H

    2015-02-11

    The basal ganglia (BG) are implicated in many movement disorders, yet how they contribute to movement remains unclear. Using wireless in vivo recording, we measured BG output from the substantia nigra pars reticulata (SNr) in mice while monitoring their movements with video tracking. The firing rate of most nigral neurons reflected Cartesian coordinates (either x- or y-coordinates) of the animal's head position during movement. The firing rates of SNr neurons are either positively or negatively correlated with the coordinates. Using an egocentric reference frame, four types of neurons can be classified: each type increases firing during movement in a particular direction (left, right, up, down), and decreases firing during movement in the opposite direction. Given the high correlation between the firing rate and the x and y components of the position vector, the movement trajectory can be reconstructed from neural activity. Our results therefore demonstrate a quantitative and continuous relationship between BG output and behavior. Thus, a steady BG output signal from the SNr (i.e., constant firing rate) is associated with the lack of overt movement, when a stable posture is maintained by structures downstream of the BG. Any change in SNr firing rate is associated with a change in position (i.e., movement). We hypothesize that the SNr output quantitatively determines the direction, velocity, and amplitude of voluntary movements. By changing the reference signals to downstream position control systems, the BG can produce transitions in body configurations and initiate actions.

  4. Basal ganglia - thalamus and the crowning enigma

    Directory of Open Access Journals (Sweden)

    Marianela eGarcia-Munoz

    2015-11-01

    Full Text Available When Hubel (1982 referred to layer 1 of primary visual cortex as …a ‘crowning mystery’ to keep area-17 physiologists busy for years to come... he could have been talking about any cortical area. In the 80’s and 90’s there were no methods to examine this neuropile on the surface of the cortex: a tangled web of axons and dendrites from a variety of different places with unknown specificities and doubtful connections to the cortical output neurons some hundreds of microns below. Recently, three changes have made the crowning enigma less of an impossible mission: the clear presence of neurons in layer 1 (L1, the active conduction of voltage along apical dendrites and optogenetic methods that might allow us to look at one source of input at a time. For all of those reasons alone, it seems it is time to take seriously the function of L1. The functional properties of this layer will need to wait for more experiments but already L1 cells are GAD67 positive, i.e., inhibitory! They could reverse the sign of the thalamic glutamate (GLU input for the entire cortex. It is at least possible that in the near future normal activity of individual sources of L1 could be detected using genetic tools. We are at the outset of important times in the exploration of thalamic functions and perhaps the solution to the crowning enigma is within sight. Our review looks forward to that solution from the solid basis of the anatomy of the basal ganglia output to motor thalamus. We will focus on L1, its afferents, intrinsic neurons and its influence on responses of pyramidal neurons in layers 2/3 and 5. Since L1 is present in the whole cortex we will provide a general overview considering evidence mainly from the somatosensory cortex before focusing on motor cortex.

  5. A novel adaptive basal therapy based on the value and rate of change of blood glucose.

    Science.gov (United States)

    Wang, Youqing; Percival, Matthew W; Dassau, Eyal; Zisser, Howard C; Jovanovic, Lois; Doyle, Francis J

    2009-09-01

    Modern insulin pump therapy for type 1 diabetes mellitus offers the freedom to program several basal profiles that may accommodate diurnal ariability in insulin sensitivity and activity level. However, these basal profiles do not change even if a pending hypoglycemic or hyperglycemic event is foreseen. New insulin pumps could receive a direct feed of glucose values from a continuous glucose monitoring (CGM) system and could enable dynamic basal adaptation to improve glycemic control. The proposed method is a two-step procedure. After the design of an initial basal profile, an adaptation of the basal rate is suggested as a gain multiplier based on the current CGM glucose value and its rate of change (ROC). Taking the glucose value and its ROC as axes, a two-dimensional plane is divided into a nine-zone mosaic, where each zone is given a predefined basal multiplier; for example, a basal multiplier of zero indicates a recommendation to shut off the pump. The proposed therapy was evaluated on 20 in silico subjects (ten adults and ten adolescents) in the Food and Drug Administration-approved UVa/Padova simulator. Compared with conventional basal therapy, the proposed basal adjustment improved the percentage of glucose levels that stayed in the range of 60-180 mg/dl for all 20 subjects. In addition, the adaptive basal therapy reduced the average blood glucose index values. The proposed therapy provides the flexibility to account for insulin sensitivity variations that may result from stress and/or physical activities. Because of its simplicity, the proposed method could be embedded in a chip in a future artificial pancreatic beta cell or used in a "smart" insulin pump. 2009 Diabetes Technology Society.

  6. Basal serum anti-müllerian hormone and antral follicle count are predictors of ovarian response for Asian women in Singapore

    Directory of Open Access Journals (Sweden)

    Lee Mee

    2014-09-01

    Conclusion: Both basal serum AMH and AFC were reliable ovarian reserve markers for predicting poor and high ovarian response to COS in Asian women. Basal AMH was the only significant predictor for clinical pregnancy outcome.

  7. Active control system for high speed windmills

    Science.gov (United States)

    Avery, D.E.

    1988-01-12

    A pump stroke is matched to the operating speed of a high speed windmill. The windmill drives a hydraulic pump for a control. Changes in speed of a wind driven shaft open supply and exhaust valves to opposite ends of a hydraulic actuator to lengthen and shorten an oscillating arm thereby lengthening and shortening the stroke of an output pump. Diminishing wind to a stall speed causes the valves to operate the hydraulic cylinder to shorten the oscillating arm to zero. A pressure accumulator in the hydraulic system provides the force necessary to supply the hydraulic fluid under pressure to drive the actuator into and out of the zero position in response to the windmill shaft speed approaching and exceeding windmill stall speed. 4 figs.

  8. 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.)

  9. Proactive selective response suppression is implemented via the basal ganglia.

    Science.gov (United States)

    Majid, D S Adnan; Cai, Weidong; Corey-Bloom, Jody; Aron, Adam R

    2013-08-14

    In the welter of everyday life, people can stop particular response tendencies without affecting others. A key requirement for such selective suppression is that subjects know in advance which responses need stopping. We hypothesized that proactively setting up and implementing selective suppression relies on the basal ganglia and, specifically, regions consistent with the inhibitory indirect pathway for which there is scant functional evidence in humans. Consistent with this hypothesis, we show, first, that the degree of proactive motor suppression when preparing to stop selectively (indexed by transcranial magnetic stimulation) corresponds to striatal, pallidal, and frontal activation (indexed by functional MRI). Second, we demonstrate that greater striatal activation at the time of selective stopping correlates with greater behavioral selectivity. Third, we show that people with striatal and pallidal volume reductions (those with premanifest Huntington's disease) have both absent proactive motor suppression and impaired behavioral selectivity when stopping. Thus, stopping goals are used to proactively set up specific basal ganglia channels that may then be triggered to implement selective suppression. By linking this suppression to the striatum and pallidum, these results provide compelling functional evidence in humans of the basal ganglia's inhibitory indirect pathway.

  10. 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.

  11. 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.

  12. Identification of triple-negative and basal-like canine mammary carcinomas using four basal markers.

    Science.gov (United States)

    Kim, N H; Lim, H Y; Im, K S; Kim, J H; Sur, J-H

    2013-05-01

    Molecular-based classification of canine mammary carcinomas (CMCs) has been a recent research focus. In human breast cancer, triple-negative and basal-like phenotypes are distinct molecular subgroups that are known for their poor prognosis, but these tumours are not yet well defined in the dog. The aim of this study was to determine whether CMCs include triple-negative and basal-like phenotypes by immunohistochemical assessment of expression of the oestrogen receptor (OR), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and four basal markers, cytokeratin (CK) 14, CK5/6, p63 and the epidermal growth factor receptor (EGFR). In this study of 241 CMCs, 45 triple-negative tumours (OR(-), PR(-) and HER2(-)) were identified and this phenotype was associated with an unfavourable prognosis. In these tumours, the expression of CK14, CK5/6 and EGFR was related to clinicopathological parameters, while the expression of p63 was not relevant. The majority of the triple-negative tumours were of the basal-like phenotype, given that 75.6% of them expressed more than two basal markers. However, three of the basal markers were not uniformly expressed; therefore, the proportion of the basal-like phenotype was altered on the basis of the selection of the markers. Although both triple-negative and basal-like phenotypes are distinct entities in CMC, further study is needed to differentiate one from the other.

  13. 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.

  14. Cholinergic basal forebrain structures are involved in the mediation of the arousal effect of noradrenaline.

    Science.gov (United States)

    Lelkes, Zoltán; Porkka-Heiskanen, Tarja; Stenberg, Dag

    2013-12-01

    Cholinergic basal forebrain structures are implicated in cortical arousal and regulation of the sleep-wake cycle. Cholinergic neurones are innervated by noradrenergic terminals, noradrenaline excites them via alpha-1 receptors and microinjection of noradrenaline into the basal forebrain enhances wakefulness. However, it is not known to what extent the cholinergic versus non-cholinergic basal forebrain projection neurones contribute to the arousing effects of noradrenaline. To elucidate the roles of cholinergic basal forebrain structures we administered methoxamine, an alpha-1-adrenergic agonist into the basal forebrain, in intact animals and again after selective destruction of the basal forebrain cholinergic cells by 192 IgG-saporin. In eight male Han-Wistar rats implanted with electroencephalogram/electromyogram electrodes, a microdialysis probe targeted into the basal forebrain was perfused with artificial cerebrospinal fluid for 6 h on a baseline day, and with cerebrospinal fluid in the first and with methoxamine in the second 3-h period of the subsequent day. The sleep-wake activity was recorded for 24 h on both days. Saporin was then injected into the basal forebrain and 2 weeks later the same experimental schedule (with cerebrospinal fluid and methoxamine) was repeated. In the intact animals, methoxamine exhibited a robust arousing effect and non-rapid eye movement (NREM) and REM sleep was suppressed. Lesioning of the basal forebrain cholinergic neurones abolished almost completely the NREM sleep-suppressing effect of methoxamine, whereas the REM sleep-suppressing effect remained intact. Thus, the basal forebrain cholinergic neurones mediate, at least in part, cortical arousal and non-REM sleep-suppression, but they are not involved in the REM sleep-suppressing effects of noradrenaline. © 2013 European Sleep Research Society.

  15. Mouse Model for Spontaneous Basal-Like Breast Cancer%自发Basal-like乳腺癌小鼠模型研究

    Institute of Scientific and Technical Information of China (English)

    张丹芳; 孙保存; 赵秀兰; 崔艳芬; 徐少艳; 董学易; 车娜

    2011-01-01

    过程中起重要作用.%Objective: Basal-like breast cancer is very Invasive and highly metastatlc with poor prognosis. The molecular mechanisms underlying its tumorigenesis and tumor progression remain unclear, and ideal animal models are lacking. The present study aims to identify the features of spontaneous breast cancer in TA2 mice, to determine whether the mouse model is useful and relevant for human basal-like breast cancer, and to investigate the relationship among pregnancy, mouse mammary tumor virus ( MMTV), and TA2 breast cancer. Methods: Spontaneous breast cancers were collected from 84 female TA2 mice. The metastasis, morphology, and inimun-ophenotype of the TA2 mice bearing breast cancer tumors were determined using hematoxylin, eosin staining, and immunnohistocherms-try, respectively. The similarities between the basal-like breast cancers of the animals and that of the human patients were compared Electrochcmilumincsccnce immunoassay was used to detect the serum levels of estradiol ( E2 ) and progesterone in the TA2 mice (n = 10 ), the mice at dl 5 during the gestation period (n = 6 ), and the normal mice ( n = 6). The MMTV in the TA2 breast cancer cells were checked under electron microscopy ( EM ). The MMTV LTR expression in the mammary glands of the normal and the pregnant mice and the TA2 mice were determined using reverse transcriptase polymerase chain reaction. Results: The spontaneous breast cancer tissues in the TA2 mice were similar to human basal-like breast cancer in terms of biology, morphology, and phenotype. The mean age of the TA2 mice at tumorigenesis was ( 329.81 ± 95.32 ) d, and the mean frequency of delivery was (2.70 ± 1.8 ), with rapid tumor growth within the gestation period. Metastasis in the visceral organs frequently occurred in TA2 tumors. However, nodal metastasis was not found in the current research. Pulmonary metastasis was seen in 80% ( 64/80 ) of the tumors. The TA2 cancers were homologous in histomorphology. The cancer nest consisted of roundlel cells with

  16. 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.

  17. Basal Forebrain Cholinergic System and Orexin Neurons: Effects on Attention

    Science.gov (United States)

    Villano, Ines; Messina, Antonietta; Valenzano, Anna; Moscatelli, Fiorenzo; Esposito, Teresa; Monda, Vincenzo; Esposito, Maria; Precenzano, Francesco; Carotenuto, Marco; Viggiano, Andrea; Chieffi, Sergio; Cibelli, Giuseppe; Monda, Marcellino; Messina, Giovanni

    2017-01-01

    The basal forebrain (BF) cholinergic system has an important role in attentive functions. The cholinergic system can be activated by different inputs, and in particular, by orexin neurons, whose cell bodies are located within the postero-lateral hypothalamus. Recently the orexin-producing neurons have been proved to promote arousal and attention through their projections to the BF. The aim of this review article is to summarize the evidence showing that the orexin system contributes to attentional processing by an increase in cortical acetylcholine release and in cortical neurons activity. PMID:28197081

  18. Photodynamic therapy for basal cell skin cancer ENT-organs

    Directory of Open Access Journals (Sweden)

    V. N. Volgin

    2014-01-01

    Full Text Available Results of photodynamic therapy in 96 patients with primary and recurrent basal cell skin cancer of ENT-organs are represented. For photodynamic therapy the Russian-made photosensitizer Photoditazine at dose of 0.6–1.4 mg/kg was used. Parameters were selected taking into account type and extent of tumor and were as follows: output power – 0.1–3.0 W, power density – 0.1–1.3 W/cm2, light dose – 100–400 J/cm2. The studies showed high efficacy of treatment for primary and recurrent basal cell skin cancer of nose, ear and external auditory canal – from 87.5 to 94.7% of complete regression. Examples of efficacy of the method are represented in the article. High efficacy and good cosmetic effects allowed to make a conclusion about perspectivity of photodynamic therapy for recurrent basal cell skin cancer of ENT-organs. 

  19. Basal forebrain thermoregulatory mechanism modulates auto-regulated sleep

    Directory of Open Access Journals (Sweden)

    Hruda N Mallick

    2012-06-01

    Full Text Available Regulation of body temperature and sleep are two physiological mechanisms that are vital for our survival. Interestingly neural structures implicated in both these functions are common. These areas include the medial preoptic area, the lateral preoptic area, the ventrolateral preoptic area, the median preoptic nucleus and the medial septum, which form part of the basal forebrain.When given a choice, rats prefer to stay at an ambient temperature of 270C, though the maximum sleep was observed when they were placed at 300C. Ambient temperature around 270C should be considered as the thermoneutral temperature for rats in all sleep studies. At this temperature the diurnal oscillations of sleep and body temperature are properly expressed. The warm sensitive neurons of the preoptic area mediate the increase in sleep at 300C. Promotion of sleep during the rise in ambient temperature from 270C to 300C, serve a thermoregulatory function. Autonomous thermoregulatory changes in core body temperature and skin temperature could act as an input signal to modulate neuronal activity in sleep-promoting brain areas. The studies presented here show that the neurons of the basal forebrain play a key role in regulating sleep. Basal forebrain thermoregulatory system is a part of the global homeostatic sleep regulatory mechanism, which is auto-regulated.

  20. Catalytically highly active top gold atom on palladium nanocluster.

    Science.gov (United States)

    Zhang, Haijun; Watanabe, Tatsuya; Okumura, Mitsutaka; Haruta, Masatake; Toshima, Naoki

    2011-10-23

    Catalysis using gold is emerging as an important field of research in connection with 'green' chemistry. Several hypotheses have been presented to explain the markedly high activities of Au catalysts. So far, the origin of the catalytic activities of supported Au catalysts can be assigned to the perimeter interfaces between Au nanoclusters and the support. However, the genesis of the catalytic activities of colloidal Au-based bimetallic nanoclusters is unclear. Moreover, it is still a challenge to synthesize Au-based colloidal catalysts with high activity. Here we now present the 'crown-jewel' concept (Supplementary Fig. S1) for preparation of catalytically highly Au-based colloidal catalysts. Au-Pd colloidal catalysts containing an abundance of top (vertex or corner) Au atoms were synthesized according to the strategy on a large scale. Our results indicate that the genesis of the high activity of the catalysts could be ascribed to the presence of negatively charged top Au atoms.

  1. Identification of highly active flocculant proteins in bovine blood.

    Science.gov (United States)

    Piazza, George J; Nuñez, Alberto; Garcia, Rafael A

    2012-03-01

    Synthetic polymeric flocculants are used extensively for wastewater remediation, soil stabilization, and reduction in water leakage from unlined canals. Sources of highly active, inexpensive, renewable flocculants are needed to replace synthetic flocculants. High kaolin flocculant activity was documented for bovine blood (BB) and blood plasma with several anticoagulant treatments. BB serum also had high flocculant activity. To address the hypothesis that some blood proteins have strong flocculating activity, the BB proteins were separated by SEC. Then, the major proteins of the flocculant-active fractions were separated by SDS-PAGE. Identity of the major protein components was determined by tryptic digestion and peptide analysis by MALDI TOF MS. The sequence of selected peptides was confirmed using TOF/TOF-MS/MS fragmentation. Hemoglobin dimer (subunits α and β) was identified as the major protein component of the active fraction in BB; its high flocculation activity was confirmed by testing a commercial sample of hemoglobin. In the same manner, three proteins from blood plasma (fibrinogen, γ-globulin, α-2-macroglobulin) were found to be highly active flocculants, but bovine serum albumin, α-globulin, and β-globulin were not flocculants. On a mass basis, hemoglobin, γ-globulin, α-2-macroglobulin were as effective as anionic polyacrylamide (PAM), a widely used synthetic flocculant. The blood proteins acted faster than PAM, and unlike PAM, the blood proteins flocculants did not require calcium salts for their activity.

  2. Multiethnic Literature; Supplements for Basal Readers.

    Science.gov (United States)

    Florez-Tighe, Viola; And Others

    Children's literature can be used effectively to enrich the reading content of basal reading materials with stories and information by and about ethnic minorities. Developing an ethnic cultural web for a literary selection can stimulate language and enhance the thought processes of students. Using the webbing process, elementary school students…

  3. Traumatisk basal subaraknoidal blødning

    DEFF Research Database (Denmark)

    Lundgaard, Peter; Leth, Peter Mygind; Gregersen, Markil

    2003-01-01

    lokaliseres. Skadesmekanismen er omdiskuteret. Karrupturen kan opstå i forbindelse med brud af processus transversus atlantis eller subluksationer i halscolumna og kan indtræffe i både normale og abnorme kar. Traumatisk basal subaraknoidalblødning kan tilsyneladende opstå ved ret lette traumer, hvilket...

  4. 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.

  5. Immunosuppressive Environment in Basal Cell Carcinoma

    DEFF Research Database (Denmark)

    Omland, Silje H; 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...

  6. Basal Cell Carcinoma in The Netherlands

    NARCIS (Netherlands)

    S.C. Flohil (Sophie)

    2012-01-01

    textabstractThere are many different cutaneous malignancies, but malignant melanoma, squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) represent approximately 98% of all skin cancers.In literature, these three skin cancers are often divided into melanoma and nonmelanoma skin cancers (NMSC

  7. Parallel basal ganglia circuits for decision making.

    Science.gov (United States)

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

    2017-02-02

    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.

  8. Carbon dioxide laser surgery of basal meningiomas.

    Science.gov (United States)

    Bartal, A D; Heilbronn, Y D; Avram, J; Razon, N

    1982-02-01

    This preliminary report summarizes our results with laser surgery in patients with basal meningiomas (8 basilar and 1 intraventricular extending also into the third ventricle). Illustrative preoperative and postoperative CT scans are included. The advantages and limitations of this surgical technique are discussed briefly.

  9. Inference of the Basal epithelial phenotype in breast carcinoma from differential marker expression, using tissue microarrays in triple negative breast cancer and women younger than 35.

    Science.gov (United States)

    Nassar, Aziza; Sussman, Zachary M; Lawson, Diane; Cohen, Cynthia

    2012-09-01

    Basal-cell phenotype breast carcinoma has been associated with high-grade and metaplastic morphology, expression of basal-type cytokeratins, uniform negativity for ER and HER2, and decreased overall survival. Breast cancers occurring in young women are usually T2 disease at presentation, high-grade and of poor prognosis. We compared two groups of breast cancers, (a) ER-, PR-, HER2- (triple negative) [TNBrCa] and (b) non-triple negative breast cancers (non-TNBrCa) occurring in women under 35, using tissue microarray technology to characterize expression of the basal/myoepithelial cytokeratins (CK5/6, CK7, and CK14), luminal cytokeratins (CK8, CK18, and CK19), EGFR, p-cadherin, c-kit, p63, and p53. We also sought to identify characteristic histomorphologic features indicative of basal-like phenotype. The triple negative group showed preferential staining versus the age triple negative patients (p = 0.006). The TNBrCa have characteristic histologic features including higher tumor grade, pushing tumor border, geographic necrosis, syncytial growth pattern, brisk mitotic activity, lack of/minimal in situ component, medullary-like and metaplastic differentiation. Invasive carcinomas in women younger than 35 usually have an associated in situ component, prominent nucleoli, central acellular fibrotic zone, and infiltrative tumor border. Triple negativity for ER/PR/HER2 coupled with EGFR, c-kit, and basal/myoepithelial cytokeratins (CK5/6, CK14) expression, and distinctive histomorphologic features predict morphology consistent with basal-cell phenotype. © 2012 Wiley Periodicals, Inc.

  10. Social capital and physical activity among Croatian high school students.

    Science.gov (United States)

    Novak, D; Doubova, S V; Kawachi, I

    2016-06-01

    To examine factors associated with regular physical activity in Croatian adolescents. A cross-sectional survey among high school students was carried out in the 2013/14 school year. A survey was conducted among 33 high schools in Zagreb City, Croatia. Participants were students aged 17-18 years. The dependent variables were regular moderate to vigorous physical activity (MVPA) and overall physical activity measured by the short version of International Physical Activity Questionnaire and defined as 60 min or more of daily physical activity. The independent variables included family, neighborhood, and high school social capital. Other study covariates included: socio-economic status, self-rated health, psychological distress and nutritional status. The associations between physical activity and social capital variables were assessed separately for boys and girls through multiple logistic regression and inverse probability weighting in order to correct for missing data bias. A total of 1689 boys and 1739 girls responded to the survey. A higher percentage of boys reported performing regular vigorous and moderate physical activity (59.4%) and overall physical activity (83.4%), comparing with the girls (35.4% and 70%, respectively). For boys, high family social capital and high informal social control were associated with increased odds of regular MVPA (1.49, 95%CI: 1.18 - 1.90 and 1.26, 95%CI: 1.02 - 1.56, respectively), compared to those with low social capital. For girls, high informal social control was associated with regular overall physical activity (OR 1.38, 95% CI: 1.09 - 1.76). High social capital is associated with regular MVPA in boys and regular overall activity in girls. Intervention and policies that leverage community social capital might serve as an avenue for promotion of physical activity in youth. Copyright © 2016 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  11. Apico-basal forces exerted by apoptotic cells drive epithelium folding.

    Science.gov (United States)

    Monier, Bruno; Gettings, Melanie; Gay, Guillaume; Mangeat, Thomas; Schott, Sonia; Guarner, Ana; Suzanne, Magali

    2015-02-12

    Epithelium folding is a basic morphogenetic event that is essential in transforming simple two-dimensional epithelial sheets into three-dimensional structures in both vertebrates and invertebrates. Folding has been shown to rely on apical constriction. The resulting cell-shape changes depend either on adherens junction basal shift or on a redistribution of myosin II, which could be driven by mechanical signals. Yet the initial cellular mechanisms that trigger and coordinate cell remodelling remain largely unknown. Here we unravel the active role of apoptotic cells in initiating morphogenesis, thus revealing a novel mechanism of epithelium folding. We show that, in a live developing tissue, apoptotic cells exert a transient pulling force upon the apical surface of the epithelium through a highly dynamic apico-basal myosin II cable. The apoptotic cells then induce a non-autonomous increase in tissue tension together with cortical myosin II apical stabilization in the surrounding tissue, eventually resulting in epithelium folding. Together our results, supported by a theoretical biophysical three-dimensional model, identify an apoptotic myosin-II-dependent signal as the initial signal leading to cell reorganization and tissue folding. This work further reveals that, far from being passively eliminated as generally assumed (for example, during digit individualization), apoptotic cells actively influence their surroundings and trigger tissue remodelling through regulation of tissue tension.

  12. 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.

  13. Are the basal cells of the mammalian epididymis still an enigma?

    Science.gov (United States)

    Arrighi, S

    2014-10-01

    Basal cells are present in the columnar pseudostratified epithelium covering the epididymis of all mammalian species, which regulates the microenvironment where the functionally incompetent germ cells produced by the testis are matured and stored. Striking novelties have come from investigations on epididymal basal cells in the past 30-40 years. In addition to an earlier hypothesised scavenger role for basal cells, linked to their proven extratubular origin and the expression of macrophage antigens, basal cells have been shown to be involved in cell-cell cross-talk, as well as functioning as luminal sensors to regulate the activity of principal and clear cells. Involvement of basal cells in the regulation of electrolyte and water transport by principal cells was hypothesised. This control is suggested to be mediated by the local formation of prostaglandins. Members of the aquaporin (AQP) and/or aquaglyceroporin family (AQP3, AQP7 and AQP8) are also specifically expressed in the rat epididymal basal cells. Transport of glycerol and glycerylphosphorylcholine from the epithelium of the epididymis to the lumen in relation to sperm maturation may be mediated by AQP. Most probably basal cells collaborate to the building up of the blood-epididymis barrier through cell adhesion molecules, implying an involvement in immune control exerted towards sperm cells, which are foreigners in the environment in which they were produced.

  14. Dissociating hippocampal and basal ganglia contributions to category learning using stimulus novelty and subjective judgments.

    Science.gov (United States)

    Seger, Carol A; Dennison, Christina S; Lopez-Paniagua, Dan; Peterson, Erik J; Roark, Aubrey A

    2011-04-15

    We identified factors leading to hippocampal and basal ganglia recruitment during categorization learning. Subjects alternated between blocks of a standard trial and error category learning task and a subjective judgment task. In the subjective judgments task subjects categorized the stimulus and then instead of receiving feedback they indicated the basis of their response using 4 options: Remember: Conscious episodic memory of previous trials. Know-Automatic: Automatic, rapid response accompanied by conscious awareness of category membership. Know-Intuition: A "gut feeling" without fully conscious knowledge of category membership. Guess: Guessing. In addition, new stimuli were introduced throughout the experiment to examine effects of novelty. Categorization overall recruited both the basal ganglia and posterior hippocampus. However, basal ganglia activity was found during Know judgments (both Automatic and Intuition), whereas posterior hippocampus activity was found during Remember judgments. Granger causality mapping indicated interactions between the basal ganglia and hippocampus, with the putamen exerting directed influence on the posterior hippocampus, which in turn exerted directed influence on the posterior caudate nucleus. We also found a region of anterior hippocampus that showed decreased activity relative to baseline during categorization overall, and showed a strong novelty effect. Our results indicate that subjective measures may be effective in dissociating basal ganglia from hippocampal dependent learning, and that the basal ganglia are involved in both conscious and unconscious learning. They also indicate a dissociation within the hippocampus, in which the anterior regions are sensitive to novelty, and the posterior regions are involved in memory based categorization learning.

  15. A functional and structural investigation of the human fronto-basal volitional saccade network.

    Directory of Open Access Journals (Sweden)

    Sebastiaan F W Neggers

    Full Text Available Almost all cortical areas are connected to the subcortical basal ganglia (BG through parallel recurrent inhibitory and excitatory loops, exerting volitional control over automatic behavior. As this model is largely based on non-human primate research, we used high resolution functional MRI and diffusion tensor imaging (DTI to investigate the functional and structural organization of the human (prefrontal cortico-basal network controlling eye movements. Participants performed saccades in darkness, pro- and antisaccades and observed stimuli during fixation. We observed several bilateral functional subdivisions along the precentral sulcus around the human frontal eye fields (FEF: a medial and lateral zone activating for saccades in darkness, a more fronto-medial zone preferentially active for ipsilateral antisaccades, and a large anterior strip along the precentral sulcus activating for visual stimulus presentation during fixation. The supplementary eye fields (SEF were identified along the medial wall containing all aforementioned functions. In the striatum, the BG area receiving almost all cortical input, all saccade related activation was observed in the putamen, previously considered a skeletomotor striatal subdivision. Activation elicited by the cue instructing pro or antisaccade trials was clearest in the medial FEF and right putamen. DTI fiber tracking revealed that the subdivisions of the human FEF complex are mainly connected to the putamen, in agreement with the fMRI findings. The present findings demonstrate that the human FEF has functional subdivisions somewhat comparable to non-human primates. However, the connections to and activation in the human striatum preferentially involve the putamen, not the caudate nucleus as is reported for monkeys. This could imply that fronto-striatal projections for the oculomotor system are fundamentally different between humans and monkeys. Alternatively, there could be a bias in published reports of

  16. High disease activity is related to low levels of physical activity in patients with ankylosing spondylitis.

    Science.gov (United States)

    Fongen, Camilla; Halvorsen, Silje; Dagfinrud, Hanne

    2013-12-01

    This study aims to compare physical activity (PA) level and exercise habits in patients with ankylosing spondylitis (AS) who have high disease activity with those who have low disease activity and, further, to compare both groups with population controls. Cross-sectional study design was used. The participants include 149 patients (mean age 49.3 (SD 11.1), 61% men, 54% high disease activity) and 133 controls (mean age 52.7 (SD11.3), 58% men). PA was reported with the International PA Questionnaire-Long and results were presented as weekly energy expenditure (metabolic equivalent, MET) in different intensities, domains, and proportion reaching health enhancing physical activity (HEPA). Types of PA were registered in a structured interview. The AS Disease Activity Score was used to assess patients' disease activity. Patients with high disease activity reported significantly lower total weekly energy expenditure (MET) than patients with low disease activity and controls (p = 0.02, p = 0.01, respectively) and lower amounts of walking (p < 0.01, p = 0.02, respectively) and vigorous activity (p = 0.06, p = 0.06, respectively). Only 41% of the patients with high disease activity reached HEPA compared to 61% of the patients with low disease activity (p = 0.02). Patients in general participated less in leisure PA performed outdoor and with higher intensities (MET ≥ 6) than controls.AS patients with high disease activity had lower weekly energy expenditure in PA than patients with low disease activity and controls, and were less likely to reach HEPA than patients with low disease activity. For optimal management, health professionals should focus on physical activity in their consultations with AS patients, especially those with high disease activity.

  17. High Resolution Screening of biologically active compounds and metabolites

    NARCIS (Netherlands)

    Kool, J.

    2007-01-01

    High Resolution Screening of biologically active compounds and metabolites Jeroen Kool Biotransformation enzymes play a crucial role in the metabolism of both endogenous compounds and xenobiotics. Usually, the detoxication of these compounds by biotransformation enzymes results in harmless metab

  18. Agroforestry systems, nutrients in litter and microbial activity in soils cultivated with coffee at high altitude

    Directory of Open Access Journals (Sweden)

    Krystal de Alcantara Notaro

    2014-04-01

    Full Text Available Agroforestry systems are an alternative option for sustainable production management. These systems contain trees that absorb nutrients from deeper layers of the soil and leaf litter that help improve the soil quality of the rough terrain in high altitude areas, which are areas extremely susceptible to environmental degradation. The aim of this study was to characterize the stock and nutrients in litter, soil activity and the population of microorganisms in coffee (Coffea arabica L. plantations under high altitude agroforestry systems in the semi-arid region of the state of Pernambuco, Brazil. Samples were collected from the surface litter together with soil samples taken at two depths (0-10 and 10-20 cm from areas each subject to one of the following four treatments: agroforestry system (AS, native forest (NF, biodynamic system (BS and coffee control (CT.The coffee plantation had been abandoned for nearly 15 years and, although there had been no management or harvesting, still contained productive coffee plants. The accumulation of litter and mean nutrient content of the litter, the soil nutrient content, microbial biomass carbon, total carbon, total nitrogen, C/N ratio, basal respiration, microbial quotient, metabolic quotient and microbial populations (total bacteria, fluorescent bacteria group, total fungi and Trichoderma spp. were all analyzed. The systems thatwere exposed to human intervention (A and BS differed in their chemical attributes and contained higher levels of nutrients when compared to NF and CT. BS for coffee production at high altitude can be used as a sustainable alternative in the high altitude zones of the semi-arid region in Brazil, which is an area that is highly susceptible to environmental degradation.

  19. 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.)

  20. Murine erythrocytes contain high levels of lysophospholipase activity

    NARCIS (Netherlands)

    Kamp, J.A.F. op den; Roelofsen, B.; Sanderink, G.; Middelkoop, E.; Hamer, R.

    1984-01-01

    Murine erythrocytes were found to be unique in the high levels of lysophospholipase activity in the cytosol of these cells. The specific activity of the enzyme in the cytosol of the murine cells is 10-times higher than in the cytosol of rabbit erythrocytes and approximately three orders of magnitude

  1. 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.

  2. 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

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

    Science.gov (United States)

    Reitsma, Pamela; Doiron, Brent; Rubin, Jonathan

    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.

  4. Basal physiological parameters in domesticated tree shrews (Tupaia belangeri chinensis).

    Science.gov (United States)

    Wang, Jing; Xu, Xin-Li; Ding, Ze-Yang; Mao, Rong-Rong; Zhou, Qi-Xin; Lü, Long-Bao; Wang, Li-Ping; Wang, Shuang; Zhang, Chen; Xu, Lin; Yang, Yue-Xiong

    2013-04-01

    Establishing non-human primate models of human diseases is an efficient way to narrow the large gap between basic studies and translational medicine. Multifold advantages such as simplicity of breeding, low cost of feeding and facility of operating make the tree shrew an ideal non-human primate model proxy. Additional features like vulnerability to stress and spontaneous diabetic characteristics also indicate that the tree shrew could be a potential new animal model of human diseases. However, basal physiological indexes of tree shrew, especially those related to human disease, have not been systematically reported. Accordingly, we established important basal physiological indexes of domesticated tree shrews including several factors: (1) body weight, (2) core body temperature and rhythm, (3) diet metabolism, (4) locomotor rhythm, (5) electroencephalogram, (6) glycometabolism and (7) serum and urinary hormone level and urinary cortisol rhythm. We compared the physiological parameters of domesticated tree shrew with that of rats and macaques. Results showed that (a) the core body temperature of the tree shrew was 39.59±0.05 ℃, which was higher than that of rats and macaques; (b) Compared with wild tree shrews, with two activity peaks, domesticated tree shrews had only one activity peak from 17:30 to 19:30; (c) Compared with rats, tree shrews had poor carbohydrate metabolism ability; and (d) Urinary cortisol rhythm indicated there were two peaks at 8:00 and 17:00 in domesticated tree shrews, which matched activity peaks in wild tree shrews. These results provided basal physiological indexes for domesticated tree shrews and laid an important foundation for diabetes and stress-related disease models established on tree shrews.

  5. 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 Gi/o protein family transduces signals from a diverse group of G protein-coupled receptors (GPCRs). The observed specificity of Gi/o-GPCR coupling and the high rate of Gi/o signal transduction have been hypothesized to be enabled by the existence of stable associates between Gi/o proteins and their cognate GPCRs in the inactive state (Gi/o-GPCR preassembly). To test this hypothesis, we applied the recently developed technique of two-photon polarization microscopy (2PPM) to Gαi1 subunits labeled with fluorescent proteins and four GPCRs: the α2A-adrenergic receptor, GABAB, cannabinoid receptor type 1 (CB1R), and dopamine receptor type 2. Our experiments with non-dissociating mutants of fluorescently labeled Gαi1 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 Gαi1 subunits and α2A-adrenergic receptor, GABAB, or dopamine receptor type 2 receptors did not reveal any interaction between the Gi1 protein and the non-stimulated GPCRs. In contrast, non-stimulated CB1R exhibited an interaction with the Gi1 protein. Further experiments revealed that this interaction is caused solely by CB1R basal activity; no preassembly between CB1R and the Gi1 protein could be observed. Our results demonstrate that four diverse GPCRs do not preassemble with non-active Gi1 However, we also show that basal GPCR activity allows interactions between non-stimulated GPCRs and Gi1 (basal coupling). These findings suggest that Gi1 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.

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

    Directory of Open Access Journals (Sweden)

    R. W. Jacobel

    2010-08-01

    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.

  7. 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.

  8. The physical activity climate in Minnesota middle and high schools.

    Science.gov (United States)

    Samuelson, Anne; Lytle, Leslie; Pasch, Keryn; Farbakhsh, Kian; Moe, Stacey; Sirard, John Ronald

    2010-11-01

    This article describes policies, practices, and facilities that form the physical activity climate in Minneapolis/St. Paul, Minnesota metro area middle and high schools and examines how the physical activity climate varies by school characteristics, including public/private, school location and grade level. Surveys examining school physical activity practices, policies and environment were administered to principals and physical education department heads from 115 middle and high schools participating in the Transdisciplinary Research on Energetics and Cancer-Identifying Determinants of Eating and Activity (TREC-IDEA) study. While some supportive practices were highly prevalent in the schools studied (such as prohibiting substitution of other classes for physical education); other practices were less common (such as providing opportunity for intramural (noncompetitive) sports). Public schools vs. private schools and schools with a larger school enrollment were more likely to have a school climate supportive of physical activity. Although schools reported elements of positive physical activity climates, discrepancies exist by school characteristics. Of note, public schools were more than twice as likely as private schools to have supportive physical activity environments. Establishing more consistent physical activity expectations and funding at the state and national level is necessary to increase regular school physical activity.

  9. 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

  10. 78 FR 70567 - Nationwide Use of High Frequency and Ultra High Frequency Active SONAR Technology; Final...

    Science.gov (United States)

    2013-11-26

    ...] Nationwide Use of High Frequency and Ultra High Frequency Active SONAR Technology; Final Programmatic... Programmatic Environmental Assessment (PEA) for the Nationwide Use of High Frequency (HF) and Ultra High Frequency (UHF) Sound Navigation and Ranging (SONAR) Technology and Finding of No Significant Impact (FONSI...

  11. Effect of simultaneous use of highly active antiretroviral therapy on survival of HIV patients with tuberculosis.

    Science.gov (United States)

    Velasco, Maria; Castilla, Virgilio; Sanz, José; Gaspar, Gabriel; Condes, Emilia; Barros, Carlos; Cervero, Miguel; Torres, Rafael; Guijarro, Carlos

    2009-02-01

    The optimal timing for initiation of highly active antiretroviral therapy (HAART) in patients with AIDS and tuberculosis (TB) is an unresolved question. To assess the effect of HAART on the survival of patients with TB, we designed this study. We selected all HIV patients included in the COMESEM cohort with TB diagnosis after 1996. Clinical and epidemiological data were registered. We compared patients who started HAART at the diagnosis of TB [simultaneous therapy (ST)] or not. Survival was assessed by Cox analysis. Among the 6934 HIV patients included in the cohort, 1217 patients had TB, 322 of them (26.5%) after 1996. At the time of TB diagnosis, 45% of them started HAART (ST). There were no differences between groups regarding basal characteristics, except for a lower viral load in ST patients. ST therapy was associated with improved survival (hazard ratio 0.38; 95% confidence interval 0.20 to 0.72, P = 0.003). By univariate analysis, survival was also associated with no endovenous drug use and a later year of TB diagnosis. After adjusting for other prognostic variables, by Cox multivariate analysis, ST remained robustly associated with improved survival (hazard ratio 0.37; 95% confidence interval 0.17 to 0.66, P = 0.001). Simultaneous HAART and TB treatment in HIV patients with TB is associated with improved survival.

  12. Kinematics of syn- and post-exhumational shear zones at Lago di Cignana (Western Alps, Italy): constraints on the exhumation of Zermatt-Saas (ultra)high-pressure rocks and deformation along the Combin Fault and Dent Blanche Basal Thrust

    Science.gov (United States)

    Kirst, Frederik; Leiss, Bernd

    2017-01-01

    Kinematic analyses of shear zones at Lago di Cignana in the Italian Western Alps were used to constrain the structural evolution of units from the Piemont-Ligurian oceanic realm (Zermatt-Saas and Combin zones) and the Adriatic continental margin (Dent Blanche nappe) during Palaeogene syn- and post-exhumational deformation. Exhumation of Zermatt-Saas (U)HP rocks to approximately lower crustal levels at ca. 39 Ma occurred during normal-sense top-(S)E shearing under epidote-amphibolite-facies conditions. Juxtaposition with the overlying Combin zone along the Combin Fault at mid-crustal levels occurred during greenschist-facies normal-sense top-SE shearing at ca. 38 Ma. The scarcity of top-SE kinematic indicators in the hanging wall of the Combin Fault probably resulted from strain localization along the uppermost Zermatt-Saas zone and obliteration by subsequent deformation. A phase of dominant pure shear deformation around 35 Ma affected units in the direct footwall and hanging wall of the Combin Fault. It is interpreted to reflect NW-SE crustal elongation during updoming of the nappe stack as a result of underthrusting of European continental margin units and the onset of continental collision. This phase was partly accompanied and followed by ductile bulk top-NW shearing, especially at higher structural levels, which transitioned into semi-ductile to brittle normal-sense top-NW deformation due to Vanzone phase folding from ca. 32 Ma onwards. Our structural observations suggest that syn-exhumational deformation is partly preserved within units and shear zones exposed at Lago di Cignana but also that the Combin Fault and Dent Blanche Basal Thrust experienced significant post-exhumational deformation reworking and overprinting earlier structures.

  13. The Basal Ganglia as a Substrate for the Multiple Actions of Amphetamines

    OpenAIRE

    Natarajan, Reka; Yamamoto, Bryan K.

    2011-01-01

    Amphetamines are psychostimulant drugs with high abuse potential. Acute and chronic doses of amphetamines affect dopamine (DA) neurotransmission in the basal ganglia. The basal ganglia are a group of subcortical nuclei that are anatomically positioned to integrate cognitive, motor and sensorimotor inputs from the cortex. Amphetamines can differentially alter the functioning of specific BG circuits to produce neurochemical changes that affect cognition, movement, and drug seeking behavior thro...

  14. Neurochemical oscillations in the basal ganglia.

    Science.gov (United States)

    Noori, Hamid Reza; Jäger, Willi

    2010-01-01

    This work represents an attempt to elucidate the neurochemical processes in the basal ganglia by mathematical modelling. The correlation between neurochemistry and electrophysiology has been used to construct a dynamical system based on the basal ganglia's network structure. Mathematical models were constructed for different physical scales to reformulate the neurochemical and electrophysiological behaviour from synapses up to multi-compartment systems. Transformation functions have been developed to transit between the different scales. We show through numerical simulations that this network produces oscillations in the electrical potentials as well as in neurotransmitter concentrations. In agreement with pharmacological experiments, a parameter sensitivity analysis reveals temporary changes in the neurochemical and electrophysiological systems after single exposure to antipsychotic drugs. This behaviour states the structural stability of the system. The correlation between the neurochemical dynamics and drug-induced behaviour provides the perspective for novel neurobiological hypotheses.

  15. 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.

  16. ATG12-ATG3 connects basal autophagy and late endosome function.

    Science.gov (United States)

    Murrow, Lyndsay; Debnath, Jayanta

    2015-01-01

    In addition to supporting cell survival in response to starvation or stress, autophagy promotes basal protein and organelle turnover. Compared to our understanding of stress-induced autophagy, little is known about how basal autophagy is regulated and how its activity is coordinated with other cellular processes. We recently identified a novel interaction between the ATG12-ATG3 conjugate and the ESCRT-associated protein PDCD6IP/Alix that promotes basal autophagy and endolysosomal trafficking. Moreover, ATG12-ATG3 is required for diverse PDCD6IP-mediated functions including late endosome distribution, exosome secretion, and viral budding. Our results highlight the importance of late endosomes for basal autophagic flux and reveal distinct roles for the core autophagy proteins ATG12 and ATG3 in controlling late endosome function.

  17. 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.

  18. Bilateral germinoma of the basal ganglia.

    Science.gov (United States)

    Rossi, Andrea; Garrè, Maria Luisa; Ravegnani, Marcello; Nozza, Paolo; Abbruzzese, Arturo; Giangaspero, Felice; Tortori-Donati, Paolo

    2008-01-01

    Germinoma arising in the bilateral basal ganglia is exceedingly rare, with only five cases reported to date. Owing to non-specific clinical findings and the frequent presence of ill-defined abnormalities without a definite tumor mass on neuroimaging, the diagnosis can be difficult. We describe a case in which magnetic resonance spectroscopy (MRS) findings suggested a tumor and supported the decision to perform biopsy of the lesion.

  19. The role of the basal ganglia in beat perception: neuroimaging and neuropsychological investigations.

    Science.gov (United States)

    Grahn, Jessica A

    2009-07-01

    Perception of musical rhythms is culturally universal. Despite this special status, relatively little is known about the neurobiology of rhythm perception, particularly with respect to beat processing. Findings are presented here from a series of studies that have specifically examined the neural basis of beat perception, using functional magnetic resonance imaging (fMRI) and studying patients with Parkinson's disease. fMRI data indicate that novel beat-based sequences robustly activate the basal ganglia when compared to irregular, nonbeat sequences. Furthermore, although most healthy participants find it much easier to discriminate changes in beat-based sequences compared to irregular sequences, Parkinson's disease patients fail to show the same degree of benefit. Taken together, these data suggest that the basal ganglia are performing a crucial function in beat processing. The results of an additional fMRI study indicate that the role of the basal ganglia is strongly linked to internal generation of the beat. Basal ganglia activity is greater when participants listen to rhythms in which internal generation of the beat is required, as opposed to rhythms with strongly externally cued beats. Functional connectivity between part of the basal ganglia (the putamen) and cortical motor areas (premotor and supplementary motor areas) is also higher during perception of beat rhythms compared to nonbeat rhythms. Increased connectivity between cortical motor and auditory areas is found in those with musical training. The findings from these converging methods strongly implicate the basal ganglia in processing a regular beat, particularly when internal generation of the beat is required.

  20. Experimental conditions affecting functional comparison of highly active glutathione transferases.

    Science.gov (United States)

    Fedulova, Natalia; Mannervik, Bengt

    2011-06-01

    Glutathione transferases (GSTs, EC 2.5.1.18) possess multiple functions and have potential applications in biotechnology. Direct evidence of underestimation of activity of human GST A3-3 and porcine GST A2-2 measured at submicromolar enzyme concentrations is reported here for the first time. The combination of time-dependent and enzyme concentration-dependent loss of activity and the choice of the organic solvent for substrates were found to cause irreproducibility of activity measurements of GSTs. These effects contribute to high variability of activity values of porcine GST A2-2 and human Alpha-class GSTs reported in the literature. Adsorption of GSTs to surfaces was found to be the main explanation of the observed phenomena. Several approaches to improved functional comparison of highly active GSTs are proposed.

  1. High Power VCSEL Device with Periodic Gain Active Region

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    High power vertical cavity surface emitting lasers(VCSEKLs) with large aperture have been fabricated through improving passivation, lateral oxidation and heat dissipation techniques. Different from conventional three quantum well structures, a periodic gain active region with nine quantum wells was incorporated into the VCSEL structure, with which high efficiency and high power operation were expected. The nine quantum wells were divided into three groups with each of them located at the antinodes of the ca...

  2. West Antarctic Mantle Plume Hypothesis and Basal Water Generation

    Science.gov (United States)

    Ivins, Erik; Seroussi, Helene; Wiens, Doug; Bondzio, Johannes

    2017-04-01

    The hypothesis of a deep mantle plume that manifests Pliocene and Quaternary volcanism and present-day seismicity in West Antarctica has been speculated for more than 30 years. Recent seismic images support the plume hypothesis as the cause of Marie Byrd Land (MBL) volcanism and geophysical structure [ Lloyd et al., 2015; Ramirez et al., 2016]. Mantle plumes can more that double the geothermal heat flux, qGHF, above nominal continental values at their axial peak position and raise qGHF in the surrounding plume head to 60 mW/m2 or higher. Unfortunately, there is a dearth of in-situ basal ice sheet data that sample the heat flux. Consequently, we examine a realistic distribution of heat flux associated with a late-Cenozoic mantle plume in West Antarctica and explore its impact on thermal and melt conditions near the ice sheet base. The solid Earth model assumes a parameterized deep mantle plume and head. The 3-D ice flow model includes an enthalpy framework and full-Stokes stress balance. Both the putative plume location and extent are uncertain. Therefore, we perform broadly scoped experiments to characterize plume related basal conditions. The experiments show that mantle plumes have an important local impact on the ice sheet, with basal melting rates reaching several centimeters per year directly above the hotspot. The downstream active lake system of Whillans Ice Stream suggests a rift-related source of anomalous mantle heat. However, the lack of lake and stream activity in MBL suggests a relatively weak plume: one that delivers less flux by 35% below the heat flux to the crustal surface at the site of the Yellowstone hotspot [e.g., DeNosaquo et al., 2009], with peak value no higher than about 145 mW/m2.

  3. Mediator is an intrinsic component of the basal RNA polymerase II machinery in vivo.

    Science.gov (United States)

    Lacombe, Thierry; Poh, Siew Lay; Barbey, Régine; Kuras, Laurent

    2013-11-01

    Mediator is a prominent multisubunit coactivator that functions as a bridge between gene-specific activators and the basal RNA polymerase (Pol) II initiation machinery. Here, we study the poorly documented role of Mediator in basal, or activator-independent, transcription in vivo. We show that Mediator is still present at the promoter when the Pol II machinery is recruited in the absence of an activator, in this case through a direct fusion between a basal transcription factor and a heterologous DNA binding protein bound to the promoter. Moreover, transcription resulting from activator-independent recruitment of the Pol II machinery is impaired by inactivation of the essential Mediator subunit Med17 due to the loss of Pol II from the promoter. Our results strongly support that Mediator is an integral component of the minimal machinery essential in vivo for stable Pol II association with the promoter.

  4. 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

  5. Super-SERS-active and highly effective antimicrobial Ag nanodendrites

    Science.gov (United States)

    Li, H. B.; Liu, P.; Liang, Y.; Xiao, J.; Yang, G. W.

    2012-07-01

    We have developed simple and green electrochemistry to synthesize Ag nanostructures with high purity, good crystallinity and smooth surface for applications as super-SERS (surface-enhanced Raman scattering), SERS-active substrates and with highly effective antimicrobial activities. This synthesis takes place in a clean and slow reaction environment without any chemical additives, which ensures an ultrahigh active surface of the as-synthesized Ag nanostructures owing to their purity, good crystallinity and smooth morphology. Using this method, we synthesized nearly perfect Ag nanodendrites (NDs), which exhibit super-SERS sensitivity when they are used to detect the SERS spectra of rhodamine 6G at concentrations as low as 5 × 10-16 M, and have an ultrahigh electromagnetic (EM) enhancement factor of the order of 1013, breaking through the theoretical limit of EM enhancement. Meanwhile, the as-synthesized Ag NDs possess highly effective antimicrobial activities for Escherichia coli, Candida albicans and Staphylococcus aureus, which are over 10 times that of silver nanoparticles. Additionally, the basic physics and chemistry involved in the fabrication of Ag nanostructures are pursued. These investigations show that silver nanostructures with highly active surfaces can make the most of Ag nanostructures functioning as super-SERS-active substrates and multiple antibiotics.

  6. Basal cell carcinomas in elderly patients treated by cryotherapy

    OpenAIRE

    Chiriac A.; Mihaila D.; Foia L; Solovan C

    2013-01-01

    Anca Chiriac,1 Doina Mihaila,2 Liliana Foia,3, Caius Solovan4 1Department of Dermatology, Nicolina Medical Center, 2Department of Pathology, St Maria Children's Hospital, 3Surgical Department, Grigore T Popa University of Medicine and Pharmacy, Iaşi, Romania; 4Victor Babe University of Medicine, Timişoara, Romania Abstract: Basal cell carcinoma is a malignant skin tumor with high incidence in our country, especially in rural areas, on sun-exposed skin (particularly on the face) in ...

  7. Basal cell adenoma of the parotid gland. Case report and review of the literature.

    Science.gov (United States)

    González-García, Raúl; Nam-Cha, Syong H; Muñoz-Guerra, Mario F; Gamallo-Amat, C

    2006-03-01

    Basal cell adenoma of the salivary glands is an uncommon type of monomorphous adenoma. Its most frequent location is the parotid gland. It usually appears as a firm and mobile slow-growing mass. Histologically, isomorphic cells in nests and interlaced trabecules with a prominent basal membrane are observed. It is also characterized by the presence of a slack and hyaline stroma and the absence of myxoid or condroid stroma. In contrast to pleomorphic adenoma, it tends to be multiple and its recurrence rate after surgical excision is high. Due to prognostic implications, differential diagnosis with basal cell adenocarcinoma, adenoid cystic carcinoma and basaloid squamous cell carcinoma is mandatory. We describe a case of basal cell adenoma of the parotid gland. We also review the literature and discuss the diagnosis and management of this rare entity.

  8. Genetics Home Reference: familial idiopathic basal ganglia calcification

    Science.gov (United States)

    ... idiopathic basal ganglia calcification ( FIBGC , formerly known as Fahr disease) is a condition characterized by abnormal deposits of ... on chromosome 14q for idiopathic basal ganglia calcification (Fahr disease). Am J Hum Genet. 1999 Sep;65(3): ...

  9. School day segmented physical activity patterns of high and low active children

    Science.gov (United States)

    2012-01-01

    Background Variability exists in children’s activity patterns due to the association with environmental, social, demographic, and inter-individual factors. This study described accelerometer assessed physical activity patterns of high and low active children during segmented school week days whilst controlling for potential correlates. Methods Two hundred and twenty-three children (mean age: 10.7 ± 0.3 yrs, 55.6% girls, 18.9% overweight/obese) from 8 north-west England primary schools wore ActiGraph GT1M accelerometers for 7 consecutive days during autumn of 2009. ActiGraph counts were converted to minutes of moderate (MPA), vigorous (VPA) and moderate-to-vigorous (MVPA) physical activity. Children were classified as high active (HIGH) or low active (LOW) depending on the percentage of week days they accumulated at least 60 minutes of MVPA. Minutes spent in MPA and VPA were calculated for school time and non-school time and for five discrete school day segments (before-school, class time, recess, lunchtime, and after-school). Data were analysed using multi-level modelling. Results The HIGH group spent significantly longer in MPA and/or VPA before-school, during class time, lunchtime, and after-school (P children, playground area per student, and temperature, depending on the segment analysed. The additive effect of the segment differences was that the HIGH group accumulated 12.5 minutes per day more MVPA than the LOW group. Conclusions HIGH active children achieved significantly more MPA and VPA than LOW active during four of the five segments of the school day when analyses were adjusted for potential correlates. Physical activity promotion strategies targeting low active children during discretionary physical activity segments of the day, and particularly via structured afterschool physical activity programs may be beneficial. PMID:22672654

  10. School day segmented physical activity patterns of high and low active children.

    Science.gov (United States)

    Fairclough, Stuart J; Beighle, Aaron; Erwin, Heather; Ridgers, Nicola D

    2012-06-06

    Variability exists in children's activity patterns due to the association with environmental, social, demographic, and inter-individual factors. This study described accelerometer assessed physical activity patterns of high and low active children during segmented school week days whilst controlling for potential correlates. Two hundred and twenty-three children (mean age: 10.7 ± 0.3 yrs, 55.6% girls, 18.9% overweight/obese) from 8 north-west England primary schools wore ActiGraph GT1M accelerometers for 7 consecutive days during autumn of 2009. ActiGraph counts were converted to minutes of moderate (MPA), vigorous (VPA) and moderate-to-vigorous (MVPA) physical activity. Children were classified as high active (HIGH) or low active (LOW) depending on the percentage of week days they accumulated at least 60 minutes of MVPA. Minutes spent in MPA and VPA were calculated for school time and non-school time and for five discrete school day segments (before-school, class time, recess, lunchtime, and after-school). Data were analysed using multi-level modelling. The HIGH group spent significantly longer in MPA and/or VPA before-school, during class time, lunchtime, and after-school (P children, playground area per student, and temperature, depending on the segment analysed.The additive effect of the segment differences was that the HIGH group accumulated 12.5 minutes per day more MVPA than the LOW group. HIGH active children achieved significantly more MPA and VPA than LOW active during four of the five segments of the school day when analyses were adjusted for potential correlates. Physical activity promotion strategies targeting low active children during discretionary physical activity segments of the day, and particularly via structured afterschool physical activity programs may be beneficial.

  11. School day segmented physical activity patterns of high and low active children

    Directory of Open Access Journals (Sweden)

    Fairclough Stuart J

    2012-06-01

    Full Text Available Abstract Background Variability exists in children’s activity patterns due to the association with environmental, social, demographic, and inter-individual factors. This study described accelerometer assessed physical activity patterns of high and low active children during segmented school week days whilst controlling for potential correlates. Methods Two hundred and twenty-three children (mean age: 10.7 ± 0.3 yrs, 55.6% girls, 18.9% overweight/obese from 8 north-west England primary schools wore ActiGraph GT1M accelerometers for 7 consecutive days during autumn of 2009. ActiGraph counts were converted to minutes of moderate (MPA, vigorous (VPA and moderate-to-vigorous (MVPA physical activity. Children were classified as high active (HIGH or low active (LOW depending on the percentage of week days they accumulated at least 60 minutes of MVPA. Minutes spent in MPA and VPA were calculated for school time and non-school time and for five discrete school day segments (before-school, class time, recess, lunchtime, and after-school. Data were analysed using multi-level modelling. Results The HIGH group spent significantly longer in MPA and/or VPA before-school, during class time, lunchtime, and after-school (P P  The additive effect of the segment differences was that the HIGH group accumulated 12.5 minutes per day more MVPA than the LOW group. Conclusions HIGH active children achieved significantly more MPA and VPA than LOW active during four of the five segments of the school day when analyses were adjusted for potential correlates. Physical activity promotion strategies targeting low active children during discretionary physical activity segments of the day, and particularly via structured afterschool physical activity programs may be beneficial.

  12. A Graphene Composite Material with Single Cobalt Active Sites: A Highly Efficient Counter Electrode for Dye-Sensitized Solar Cells.

    Science.gov (United States)

    Cui, Xiaoju; Xiao, Jianping; Wu, Yihui; Du, Peipei; Si, Rui; Yang, Huaixin; Tian, Huanfang; Li, Jianqi; Zhang, Wen-Hua; Deng, Dehui; Bao, Xinhe

    2016-06-01

    The design of catalysts that are both highly active and stable is always challenging. Herein, we report that the incorporation of single metal active sites attached to the nitrogen atoms in the basal plane of graphene leads to composite materials with superior activity and stability when used as counter electrodes in dye-sensitized solar cells (DSSCs). A series of composite materials based on different metals (Mn, Fe, Co, Ni, and Cu) were synthesized and characterized. Electrochemical measurements revealed that CoN4 /GN is a highly active and stable counter electrode for the interconversion of the redox couple I(-) /I3 (-) . DFT calculations revealed that the superior properties of CoN4 /GN are due to the appropriate adsorption energy of iodine on the confined Co sites, leading to a good balance between adsorption and desorption processes. Its superior electrochemical performance was further confirmed by fabricating DSSCs with CoN4  /GN electrodes, which displayed a better power conversion efficiency than the Pt counterpart.

  13. Basal ganglia infarction demonstrated by radionuclide brain imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kim, E.E.; Schacht, R.A.; Domstad, P.A.; DeLand, F.H.

    1982-11-01

    Four cases of basal ganglia infarction demonstrated by radionuclide brain imaging are presented. Bilateral basal ganglia infarctions in two patients were probably related to methanol intoxication and meningoencephalitis, and unilateral basal ganglia infarctions in two other patients were presumably due to cerebral atherosclerosis and/or hypertension. Various causes and mechanisms of basal ganglia infarction as well as positive findings of radionuclide brain imaging are briefly reviewed.

  14. Basal autophagy protects cardiomyocytes from doxorubicin-induced toxicity.

    Science.gov (United States)

    Pizarro, Marcela; Troncoso, Rodrigo; Martínez, Gonzalo J; Chiong, Mario; Castro, Pablo F; Lavandero, Sergio

    2016-08-31

    Doxorubicin (Doxo) is one of the most effective anti-neoplastic agents but its cardiotoxicity has been an important clinical limitation. The major mechanism of Doxo-induced cardiotoxicity is associated to its oxidative capacity. However, other processes are also involved with significant consequences for the cardiomyocyte. In recent years, a number of studies have investigated the role of autophagy on Doxo-induced cardiotoxicity but to date it is not clear how Doxo alters that process and its consequence on cardiomyocytes viability. Here we investigated the effect of Doxo 1uM for 24h of stimulation on cultured neonatal rat cardiomyocytes. We showed that Doxo inhibits basal autophagy. This inhibition is due to both Akt/mTOR signaling pathway activation and Beclin 1 level decrease. To assess the role of autophagy on Doxo-induced cardiomyocyte death, we evaluated the effects 3-methyladenine (3-MA), bafilomycin A1 (BafA), siRNA Beclin 1 (siBeclin 1) and rapamycin (Rapa) on cell viability. Inhibition of autophagy with 3-MA, BafA and siBeclin 1 increased lactate dehydrogenase (LDH) release but, when autophagy was induced by Rapa, Doxo-induced cardiomyocyte death was decreased. These results suggest that Doxo inhibits basal autophagy and contributes to cardiomyocyte death. Activation of autophagy could be used as a strategy to protect the heart against Doxo toxicity.

  15. Recommendations of activity restriction in high-risk pregnancy scenarios

    DEFF Research Database (Denmark)

    Bendix, Jane; Hegaard, Hanne Kristine; Bergholt, Thomas;

    2015-01-01

    obstetricians and midwives prescribe activity restriction in most high-risk pregnancies. The degree of activity restriction and the presumed effect vary between clinicians. This may reflect different attitudes and lack of guidelines based on clinical studies of a possible benefit of activity restriction....... to the obstetricians, the midwives also reported that they expected the recommendation to be more effective. Most midwives and obstetricians reported that they thought strict activity restriction was associated with severe or moderate adverse effect, and recommended antithrombotic prophylaxis. Conclusions: Danish......Abstract Aims: To describe specific recommendations of activity restriction, place of care, expected beneficial and adverse effects, and recommended antithrombotic prophylaxis in nine clinical scenarios. Methods: A national survey. All members of the Danish Society of Obstetrics and Gynaecology...

  16. Combining basal insulin analogs with glucagon-like peptide-1 mimetics.

    Science.gov (United States)

    Perfetti, Riccardo

    2011-09-01

    Basal insulin analogs are recognized as an effective method of achieving and maintaining glycemic control for patients with type 2 diabetes. However, the progressive nature of the disease means that some individuals may require additional ways to maintain their glycemic goals. Intensification in these circumstances has traditionally been achieved by the addition of short-acting insulin to cover postprandial glucose excursions that are not targeted by basal insulin. However, intensive insulin regimens are associated with a higher risk of hypoglycemia and weight gain, which can contribute to a greater burden on patients. The combination of basal insulin with a glucagon-like peptide-1 (GLP-1) mimetic is a potentially attractive solution to this problem for some patients with type 2 diabetes. GLP-1 mimetics target postprandial glucose and should complement the activity of basal insulins; they are also associated with a relatively low risk of associated hypoglycemia and moderate, but significant, weight loss. Although the combination has not been approved by regulatory authorities, preliminary evidence from mostly small-scale studies suggests that basal insulins in combination with GLP-1 mimetics do provide improvements in A1c and postprandial glucose with concomitant weight loss and no marked increase in the risk of hypoglycemia. These results are promising, but further studies are required, including comparisons with basal-bolus therapy, before the complex value of this association can be fully appreciated.

  17. Direct visualization of spruce budworm antifreeze protein interacting with ice crystals: basal plane affinity confers hyperactivity.

    Science.gov (United States)

    Pertaya, Natalya; Marshall, Christopher B; Celik, Yeliz; Davies, Peter L; Braslavsky, Ido

    2008-07-01

    Antifreeze proteins (AFPs) protect certain organisms from freezing by adhering to ice crystals, thereby preventing their growth. All AFPs depress the nonequilibrium freezing temperature below the melting point; however AFPs from overwintering insects, such as the spruce budworm (sbw) are 10-100 times more effective than most fish AFPs. It has been proposed that the exceptional activity of these AFPs depends on their ability to prevent ice growth at the basal plane. To test the hypothesis that the hyperactivity of sbwAFP results from direct affinity to the basal plane, we fluorescently tagged sbwAFP and visualized it on the surface of ice crystals using fluorescence microscopy. SbwAFP accumulated at the six prism plane corners and the two basal planes of hexagonal ice crystals. In contrast, fluorescently tagged fish type III AFP did not adhere to the basal planes of a single-crystal ice hemisphere. When ice crystals were grown in the presence of a mixture of type III AFP and sbwAFP, a hybrid crystal shape was produced with sbwAFP bound to the basal planes of truncated bipyramidal crystals. These observations are consistent with the blockage of c-axial growth of ice as a result of direct interaction of sbwAFP with the basal planes.

  18. 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

  19. High lightning activity in maritime clouds near Mexico

    Directory of Open Access Journals (Sweden)

    B. Kucienska

    2012-01-01

    Full Text Available Lightning activity detected by the World Wide Lightning Location Network (WWLLN over oceanic regions adjacent to Mexico is often as high as that observed over the continent. In order to explore the possible cause of the observed high flash density over those regions, the relationships between lightning, rainfall, vertical hydrometeor profiles, latent heating, wind variability and aerosol optical thickness are analyzed. The characteristics of lightning and precipitation over four oceanic zones adjacent to Mexican coastlines are contrasted against those over the continent. In addition, we compare two smaller regions over the Tropical Pacific Ocean: one located within the Inter-Tropical Converge Zone and characterized by high rainfall and weak lightning activity and the other influenced by a continental jet and presenting high rainfall and strong lightning activity over the Gulf of Tehuantepec. Maritime precipitating clouds that develop within the region influenced by offshore winds exhibit similar properties to continental clouds: large content of precipitation ice and an increased height range of coexistence of precipitation ice and cloud water. During the rainy season, monthly distribution of lightning within the region influenced by the continental jet is contrary to that of rainfall. Moreover, the monthly variability of lightning is very similar to the variability of the meridional wind component and it is also related to the variability of aerosol optical depth. The analysis strongly suggests that the high lightning activity observed over the Gulf of Tehuantepec is caused by continental cloud condensation nuclei advected over the ocean.

  20. Expression of stromelysin 3 in basal cell carcinomas.

    Science.gov (United States)

    Cribier, B; Noacco, G; Peltre, B; Grosshans, E

    2001-01-01

    Stromelysin 3 is a member of the metalloproteinase family, which is expressed in various remodelling processes. The prognosis of breast cancers and squamous cell carcinomas is correlated to the level of expression of this protein. The purpose of the present work was to evaluate the expression of stromelysin 3 in the major types of basal cell carcinomas. We selected cases of primary tumours that were fully excised, without previous biopsy: 40 Pinkus tumors, 40 superficial, 40 nodular, 38 morpheiform basal cell carcinomas and 10 cases showing deep subcutaneous or muscular invasion. Immunohistochemistry was carried out using monoclonal anti-ST3 antibodies (MC Rio, IGBMC Strasbourg), and evaluated on a semi-quantitative scale from 0 to 3. Positively stained cells were restricted to the periphery of the epithelial cells, which, by contrast, never expressed stromelysin 3. The global rate of expression was 27% in Pinkus tumors, 65% in superficial, 72.5% in nodular, 87% in morpheiform and 100% in deeply invasive carcinomas. The rates of tumours showing the highest number of positively stained cells (class 2 or 3) were respectively 7.5%, 20%, 45%, 63% and 100%. This systematic study of stromelysin3 expression in basal cell carcinomas confirms that it is a marker of poor prognosis, because the rate of positive tumours was much higher in aggressive carcinomas. Moreover, the majority of tumours showing an intense expression (i.e. the highest number of positively stained cells in their stroma) were of the morpheiform and deeply invasive types, which are of poor prognosis. Altogether, the studies performed on cutaneous tumours are consistent with the theory of stromelysin 3 playing an active role in tumour progression.

  1. Mössbauer spectroscopy of Basal Ganglia

    Energy Technology Data Exchange (ETDEWEB)

    Miglierini, Marcel, E-mail: marcel.miglierini@stuba.sk [Institute of Nuclear and Physical Engineering, Faculty of Electrical Engineering and Information Technology, Slovak University of Technology, Ilkovičova 3, 812 19 Bratislava, Slovakia and Regional Centre of Advanced Technologies and Materials (Czech Republic); Lančok, Adriana [Institute of Inorganic Chemistry AS CR, v. v. i., 250 68 Husinec-Řež 1001 (Czech Republic); Kopáni, Martin [Institute of Medical Physics, Biophysics, Informatics and Telemedicine, Faculty of Medicine, Comenius University, Sasinkova 2, 811 08 Bratislava (Slovakia); Boča, Roman [Department of Chemistry, Faculty of Natural Sciences, University of SS. Cyril and Methodius, 917 01 Trnava (Slovakia)

    2014-10-27

    Chemical states, structural arrangement, and magnetic features of iron deposits in biological tissue of Basal Ganglia are characterized. The methods of SQUID magnetometry and electron microscopy are employed. {sup 57}Fe Mössbauer spectroscopy is used as a principal method of investigation. Though electron microscopy has unveiled robust crystals (1-3 μm in size) of iron oxides, they are not manifested in the corresponding {sup 57}Fe Mössbauer spectra. The latter were acquired at 300 K and 4.2 K and resemble ferritin-like behavior.

  2. Nonsurgical Treatment Options for Basal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Mary H. Lien

    2011-01-01

    Full Text Available Basal cell carcinoma (BCC remains the most common form of nonmelanoma skin cancer (NMSC in Caucasians, with perhaps as many as 2 million new cases expected to occur in the United States in 2010. Many treatment options, including surgical interventions and nonsurgical alternatives, have been utilized to treat BCC. In this paper, two non-surgical options, imiquimod therapy and photodynamic therapy (PDT, will be discussed. Both modalities have demonstrated acceptable disease control rates, cosmetically superior outcomes, and short-term cost-effectiveness. Further studies evaluating long-term cure rates and long-term cost effectiveness of imiquimod therapy and PDT are needed.

  3. Adenoid basal cell carcinoma and its mimics

    Directory of Open Access Journals (Sweden)

    Sujata Jetley

    2013-01-01

    Full Text Available Basal cell carcinoma (BCC is the most common malignant tumor of skin. The most common site (80% is head and neck. BCC exhibits a varied morphology such as adenoid, keratotic, sebaceous, basosquamous, apocrine, eccrine or fibroepithelial. Tumors with a similar histopathological picture are cutaneous adenoid cystic carcinoma and primary cutaneous cribriform apocrine carcinoma. Immunohistochemistry, along with clinical findings, acts as an adjunct in reaching an accurate diagnosis. Here, we present an interesting case of adenoid BCC in a 55-year-old man.

  4. Archaefructaceae, a new basal angiosperm family.

    Science.gov (United States)

    Sun, Ge; Ji, Qiang; Dilcher, David L; Zheng, Shaolin; Nixon, Kevin C; Wang, Xinfu

    2002-05-03

    Archaefructaceae is proposed as a new basal angiosperm family of herbaceous aquatic plants. This family consists of the fossils Archaefructus liaoningensis and A. sinensis sp. nov. Complete plants from roots to fertile shoots are known. Their age is a minimum of 124.6 million years from the Yixian Formation, Liaoning, China. They are a sister clade to all angiosperms when their characters are included in a combined three-gene molecular and morphological analysis. Their reproductive axes lack petals and sepals and bear stamens in pairs below conduplicate carpels.

  5. 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.

  6. Identifying High School Physical Education Physical Activity Patterns after High School

    Science.gov (United States)

    Barney, David; Pleban, Francis T.; Wilkinson, Carol; Prusak, Keven A.

    2015-01-01

    National standards for physical education (PE) encompass five principles for the purpose of defining what high school students should recognize and be able to perform as a result of a quality PE program. The expectation is that youth will develop an active, healthy lifestyle into adulthood from activities and skills taught in PE. Researchers from…

  7. Physical Activity in High School during "Free-Time" Periods

    Science.gov (United States)

    Silva, Pedro; Sousa, Michael; Sá, Carla; Ribeiro, José; Mota, Jorge

    2015-01-01

    The purpose of this study was to examine youth physical activity (PA) in free-time periods during high school days and their contribution to total PA. Differences in terms of sex, age, body mass index and school level were assessed in a sample of Portuguese adolescents. Participants totalled 213 (135 girls), aged 14.6 ± 1.7, from two different…

  8. High Frequency State-Variable Biquadratic Active Filters

    Directory of Open Access Journals (Sweden)

    T. Dostal

    1998-04-01

    Full Text Available The state-variable (KHN active RC biquadratic filters with good performance in high frequency range , flexibility of outputs (LP, HP, BP, low sensitivities in novel current and hybrid modes, using current conveyors, transimpedance, trans-admittance and current operational amplifiers, are given in this paper.

  9. High hydrostatic pressure treatment of porcine oocytes induces parthenogenetic activation

    DEFF Research Database (Denmark)

    Lin, Lin; Pribenszky, Csaba; Molnár, Miklós

    2010-01-01

    An innovative technique called high hydrostatic pressure (HHP) treatment has recently been reported to improve the cryosurvival of gametes and embryos in certain mammalian species, including the mouse, pig, and cattle. In the present study the parthenogenetic activation (PA) of pig oocytes caused...

  10. Reduced autonomic activity during stepwise exposure to high altitude

    NARCIS (Netherlands)

    Sevre, K; Bendz, B; Hanko, E; Nakstad, AR; Hauge, A; Kasin, JI; Lefrandt, JD; Smit, AJ; Eide, [No Value; Rostrup, M

    2001-01-01

    Several studies have shown increased sympathetic activity during acute exposure to hypobaric hypoxia. In a recent field study we found reduced plasma catecholamines during the first days after a stepwise ascent to high altitude. In the present study 14 subjects were exposed to a simulated ascent in

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

    Directory of Open Access Journals (Sweden)

    Yannick Gache

    Full Text Available 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

  12. 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.

  13. Development activities of the high heat flux scraper element

    Energy Technology Data Exchange (ETDEWEB)

    Boscary, J., E-mail: jean.boscary@ipp.mpg.de [Max Planck Institute for Plasma Physics, Garching (Germany); Lore, J.; Lumsdaine, A. [Oak Ridge National Laboratory, Oak Ridge, TN (United States); Maier, M. [Max Planck Institute for Plasma Physics, Garching (Germany); McGinnis, D. [Oak Ridge National Laboratory, Oak Ridge, TN (United States); Peacock, A.; Tretter, J. [Max Planck Institute for Plasma Physics, Garching (Germany)

    2015-10-15

    The function of the high heat flux scraper element is to reduce the heat loads on the element ends of the actively cooled divertor of Wendelstein 7-X. The scraper element is actively water cooled to remove up to 550 kW steady state power load, with localized heat fluxes as high as 20 MW/m{sup 2}. Its surface area, 0.17 m{sup 2}, is contoured to optimally intercept both upstream and downstream particle fluxes. The plasma facing surface is made of 24 individual scraper fingers based on the monoblock technology. Each scraper finger is 247 mm long and 28 mm wide and has 13 monoblocks made of CFC NB31 bonded by hot isostatic pressing onto a CuCrZr cooling tube equipped with a copper twisted tape. Development activities, described here, include the design and fabrication of prototypes to validate the different technologies selected for the scraper element design to prepare a possible production.

  14. Basal cell nevus syndrome or Gorlin syndrome.

    Science.gov (United States)

    Thalakoti, Srikanth; Geller, Thomas

    2015-01-01

    Basal cell nevus syndrome (BCNS) or Gorlin syndrome is a rare neurocutaneous syndrome sometimes known as the fifth phacomatosis, inherited in autosomal dominant fashion with complete penetrance and variable expressivity. Gorlin syndrome is characterized by development of multiple basal cell carcinomas (BCCs), jaw cysts, palmar or plantar pits, calcification of falx cerebri, various developmental skeletal abnormalities such as bifid rib, hemi- or bifid vertebra and predisposition to the development of various tumors. BCNS is caused by a mutation in the PTCH1 gene localized to 9q22.3. Its estimated prevalence varies between 1/55600 and 1/256000 with an equal male to female ratio. The medulloblastoma variant seen in Gorlin syndrome patients is of the desmoplastic type, characteristically presenting during the first 3 years of life. Therefore, children with desmoplastic medulloblastoma should be carefully screened for other features of BCNS. Radiation therapy for desmoplastic medulloblastoma should be avoided in BCNS patients as it may induce development of invasive BCCs and other tumors in the skin area exposed to radiation. This syndrome is a multisystem disorder so involvement of multiple specialists with a multimodal approach to detect and treat various manifestations at early stages will reduce the long-term sequelae and severity of the condition. Life expectancy is not significantly altered but morbidity from complications and cosmetic scarring can be substantial.

  15. Review of actuators for high speed active flow control

    Institute of Scientific and Technical Information of China (English)

    WANG Lin; LUO ZhenBing; XIA ZhiXun; LIU Bing; DENG Xiong

    2012-01-01

    Actuators are one of the key points for the development of active flow control technology.Efficient methods of high speed flow control can provide enhanced propulsive efficiency and at the same time enable safe and maneuverable high speed flight.The development of high speed flight technology promotes the emergence of novel and robust actuators.This review introduces the state of the art in the development of actuators that can be used in high speed active flow control.The classification and different operation criteria of the actuators are discussed.The specifications,mechanisms and applications of various popular actuator types including fluidic,mechanical,and plasma actuators are described.Based on the realistic need of high speed flow control and the existing results of actuators,a new actuator design method is proposed.At last,the merits and drawbacks of the actuators are summarized and some suggestions on the development of active flow control technology are put forward.

  16. High efficiency cell-specific targeting of cytokine activity

    Science.gov (United States)

    Garcin, Geneviève; Paul, Franciane; Staufenbiel, Markus; Bordat, Yann; van der Heyden, José; Wilmes, Stephan; Cartron, Guillaume; Apparailly, Florence; de Koker, Stefaan; Piehler, Jacob; Tavernier, Jan; Uzé, Gilles

    2014-01-01

    Systemic toxicity currently prevents exploiting the huge potential of many cytokines for medical applications. Here we present a novel strategy to engineer immunocytokines with very high targeting efficacies. The method lies in the use of mutants of toxic cytokines that markedly reduce their receptor-binding affinities, and that are thus rendered essentially inactive. Upon fusion to nanobodies specifically binding to marker proteins, activity of these cytokines is selectively restored for cell populations expressing this marker. This ‘activity-by-targeting’ concept was validated for type I interferons and leptin. In the case of interferon, activity can be directed to target cells in vitro and to selected cell populations in mice, with up to 1,000-fold increased specific activity. This targeting strategy holds promise to revitalize the clinical potential of many cytokines.

  17. Business cycle and innovation activity in medium-high and high technology industry in Poland

    Directory of Open Access Journals (Sweden)

    Dzikowski Piotr

    2015-12-01

    Full Text Available This article examines differences in an impact of business cycle phases on innovation activity in medium-high and high technology industry in Poland. It is assumed that each business cycle phase influences innovation activity in the same fashion, but its impact varies and it depends on the firm’s innovation activity. The higher innovation activity the less impact of business cycle. The scope of the survey relates to innovation in MHT and HT industry in Poland. The data concerns the innovation at the firm level and the diffusion “new for the company”. Innovation activity is defined by the following activities: (1 expenditure on research and development and investments in fixed assets not used so far such as: abuildings, premises and land; b machinery and equipment, c computer software; (2 implementation of new products and technological processes and (3 innovation cooperation. The methodological part of the analysis includes a logit modeling. The survey includes 1355 companies. Business cycle has a great influence on innovation activity in MTH and HT industry in Poland. The influence of recovery phase is positive whereas both stagnation and recession phases decrease the probability of innovation activity. The character of influence depends on the propensity to take innovation activity. The higher level of innovation activity the enterprises present the less influence of business cycle they get.

  18. Carcinogenesis of basal cell carcinomas: genetics and molecular mechanisms.

    Science.gov (United States)

    Lacour, J P

    2002-04-01

    Basal cell carcinoma (BCC) of the skin is the most common type of cancer in humans. Like squamous cell carcinomas, they are also believed to be ultraviolet (UV)-induced, but several data suggest that some differences might exist in the mechanisms of their UV induction. The originating cells may arise from interfollicular basal cells, hair follicles or sebaceous glands, thus from a deeper zone than the SCC ones, which probably means exposure to different doses or wavelengths of UV. The p53 gene and the patched gene (PTCH) are major targets of UV for BCC induction. Mutations in p53 are present in about 56% of human BCC, even small early lesions. The "UV signature" is observed in 65% of them. Mutations in the PTCH play also a major role in BCC development, being responsible for hereditary BCCs in Gorlin's syndrome, sporadic BCC, and BCCs isolated from xeroderma pigmentosum, although with a lower incidence of "UV signature". Smoothened-activating mutations and PTCH2 mutations are also involved in BCC formation. Transgenic mice overexpressing Smoothened or Sonic hedgehog in the skin spontaneously produce skin lesions resembling human BCCs, but contrary to findings in the hairless albino mouse and with SCC, no data on experimental UV induction of BCCs are available.

  19. Basal regulation of HPA and dopamine systems is altered differentially in males and females by prenatal alcohol exposure and chronic variable stress.

    Science.gov (United States)

    Uban, Kristina A; Comeau, Wendy L; Ellis, Linda A; Galea, Liisa A M; Weinberg, Joanne

    2013-10-01

    Effects of prenatal alcohol exposure (PAE) on central nervous system function include an increased prevalence of mental health problems, including substance use disorders (SUD). The hypothalamic-pituitary-adrenal (HPA) and dopamine (DA) systems have overlapping neurocircuitries and are both implicated in SUD. PAE alters both HPA and dopaminergic activity and regulation, resulting in increased HPA tone and an overall reduction in tonic DA activity. However, effects of PAE on the interaction between HPA and DA systems have not been investigated. The present study examined PAE effects on basal regulation of central stress and DA systems in key brain regions where these systems intersect. Adult Sprague-Dawley male and female offspring from prenatal alcohol-exposed (PAE), pairfed (PF), and ad libitum-fed control (C) groups were subjected to chronic variable stress (CVS) or remained as a no stress (non-CVS) control group. Corticotropin releasing hormone (CRH) mRNA, as well as glucocorticoid and DA receptor (DA-R) expression were measured under basal conditions 24h following the end of CVS. We show, for the first time, that regulation of basal HPA and DA systems, and likely, HPA-DA interactions, are altered differentially in males and females by PAE and CVS. PAE augmented the typical attenuation in weight gain during CVS in males and caused increased weight loss in females. Increased basal corticosterone levels in control, but not PAE, females suggest that PAE alters the profile of basal hormone secretion throughout CVS. CVS downregulated basal CRH mRNA in the prefrontal cortex and throughout the bed nucleus of the stria terminalis (BNST) in PAE females but only in the posterior BNST of control females. PAE males and females exposed to CVS exhibited more widespread upregulation of basal mineralocorticoid receptor mRNA throughout the hippocampus, and an attenuated decrease in DA-R expression throughout the nucleus accumbens and striatum compared to CVS-exposed control

  20. 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

  1. Reduced glutamine synthetase activity plays a role in control of photosynthetic responses to high light in barley leaves.

    Science.gov (United States)

    Brestic, Marian; Zivcak, Marek; Olsovska, Katarina; Shao, Hong-Bo; Kalaji, Hazem M; Allakhverdiev, Suleyman I

    2014-08-01

    The chloroplastic glutamine synthetase (GS, EC 6.3.1.2) activity was previously shown to be the limiting step of photorespiratory pathway. In our experiment, we examined the photosynthetic high-light responses of the GS2-mutant of barley (Hordeum vulgare L.) with reduced GS activity, in comparison to wild type (WT). The biophysical methods based on slow and fast chlorophyll fluorescence induction, P700 absorbance, and gas exchange measurements were employed. Despite the GS2 plants had high basal fluorescence (F0) and low maximum quantum yield (Fv/Fm), the CO2 assimilation rate, the PSII and PSI actual quantum yields were normal. On the other hand, in high light conditions the GS2 had much higher non-photochemical quenching (NPQ), caused both by enhanced capacity of energy-dependent quenching and disconnection of PSII antennae from reaction centers (RC). GS2 leaves also maintained the PSII redox poise (QA(-)/QA total) at very low level; probably this was reason why the observed photoinhibitory damage was not significantly above WT. The analysis of fast chlorophyll fluorescence induction uncovered in GS2 leaves substantially lower RC to antenna ratio (RC/ABS), low PSII/PSI ratio (confirmed by P700 records) as well as low PSII excitonic connectivity.

  2. Physical properties of highly active liquor containing molybdate solids

    Energy Technology Data Exchange (ETDEWEB)

    Dunnett, B.; Ward, T.; Roberts, R. [National Nuclear Laboratory, Sellafield, Seascale, Cumbria, CA20 1PG (United Kingdom); Cheeseright, J. [Sellafield Ltd, Sellafield, Seascale, Cumbria, CA20 1PG (United Kingdom)

    2016-07-01

    The reprocessing of irradiated nuclear fuel at Sellafield produces a nitric acid based Highly Active Liquor (HAL) waste. The liquor, containing fission products and process additives, is concentrated in an evaporator in order to reduce the volume and is then stored in Highly Active Storage Tanks (HASTs) prior to vitrification. Caesium phosphomolybdate (CPM) is precipitated during the evaporation process and can convert to zirconium molybdate (ZM) during storage. During Post Operational Clean Out (POCO) of the HASTs, it is expected that their highly active content will be reduced by repeated cycles of washing using nitric acid and other reagents. Initial washings are likely to have a chemical composition comparable to concentrated HAL, becoming more dilute during the wash-out process. It is expected that the wash-out process will also recover significant quantities of molybdate solids (ZM, CPM or a mixture) from the HASTs. In order to determine the processing challenges from such washings during POCO, the physical properties of varying concentrations of non-active HAL simulants containing molybdate solids have recently been measured by the UK's National Nuclear Laboratory. The following measurements are presented and discussed: Particle size distribution; Density; Settling behaviour of solids; Voidage of settled sediment beds; Viscosity; Yield stress; And influence of ZM morphology on physical properties. (authors)

  3. Basal Complex and Basal Venation of Odonata Wings: Structural Diversity and Potential Role in the Wing Deformation

    Science.gov (United States)

    Rajabi, H.; Ghoroubi, N.; Malaki, M.; Darvizeh, A.; Gorb, S. N.

    2016-01-01

    Dragonflies and damselflies, belonging to the order Odonata, are known to be excellent fliers with versatile flight capabilities. The ability to fly over a wide range of speeds, high manoeuvrability and great agility are a few characteristics of their flight. The architecture of the wings and their structural elements have been found to play a major role in this regard. However, the precise influence of individual wing components on the flight performance of these insects remains unknown. The design of the wing basis (so called basal complex) and the venation of this part are responsible for particular deformability and specific shape of the wing blade. However, the wing bases are rather different in representatives of different odonate groups. This presumably reflects the dimensions of the wings on one hand, and different flight characteristics on the other hand. In this article, we develop the first three-dimensional (3D) finite element (FE) models of the proximal part of the wings of typical representatives of five dragonflies and damselflies families. Using a combination of the basic material properties of insect cuticle, a linear elastic material model and a nonlinear geometric analysis, we simulate the mechanical behaviour of the wing bases. The results reveal that although both the basal venation and the basal complex influence the structural stiffness of the wings, it is only the latter which significantly affects their deformation patterns. The use of numerical simulations enabled us to address the role of various wing components such as the arculus, discoidal cell and triangle on the camber formation in flight. Our study further provides a detailed representation of the stress concentration in the models. The numerical analysis presented in this study is not only of importance for understanding structure-function relationship of insect wings, but also might help to improve the design of the wings for biomimetic micro-air vehicles (MAVs). PMID:27513753

  4. Highly porous activated carbons prepared from carbon rich Mongolian anthracite by direct NaOH activation

    Energy Technology Data Exchange (ETDEWEB)

    Byamba-Ochir, Narandalai [School of Chemical Engineering, Chonnam National University, 77 Yongbong-Ro, Gwangju 61186 (Korea, Republic of); Shim, Wang Geun [Department of Polymer Science and Engineering, Sunchon National University, 255 Jungang-Ro, Suncheon, Jeollanam-Do 57922 (Korea, Republic of); Balathanigaimani, M.S., E-mail: msbala@rgipt.ac.in [Department of Chemical Engineering, Rajiv Gandhi Institute of Petroleum Technology, Ratapur Chowk, Rae Bareli, 229316 Uttar Pradesh (India); Moon, Hee, E-mail: hmoon@jnu.ac.kr [School of Chemical Engineering, Chonnam National University, 77 Yongbong-Ro, Gwangju 61186 (Korea, Republic of)

    2016-08-30

    Highlights: • Highly porous carbon materials from Mongolian anthracite by chemical activation. • Cheaper and eco-friendly activation process has been employed. • Activated carbons with graphitic structure and energetically heterogeneous surface. • Surface hydrophobicity and porosity of the activated carbons can be controlled. - Abstract: Highly porous activated carbons (ACs) were prepared from Mongolian raw anthracite (MRA) using sodium hydroxide as an activation agent by varying the mass ratio (powdered MRA/NaOH) as well as the mixing method of chemical agent and powdered MRA. The specific BET surface area and total pore volume of the prepared MRA-based activated carbons (MACs) are in the range of 816–2063 m{sup 2}/g and of 0.55–1.61 cm{sup 3}/g, respectively. The pore size distribution of MACs show that most of the pores are in the range from large micropores to small mesopores and their distribution can be controlled by the mass ratio and mixing method of the activating agent. As expected from the intrinsic property of the MRA, the highly graphitic surface morphology of prepared carbons was confirmed from Raman spectra and transmission electron microscopy (TEM) studies. Furthermore the FTIR and XPS results reveal that the preparation of MACs with hydrophobic in nature is highly possible by controlling the mixing conditions of activating agent and powdered MRA. Based on all the results, it is suggested that the prepared MACs could be used for many specific applications, requiring high surface area, optimal pore size distribution, proper surface hydrophobicity as well as strong physical strength.

  5. Adolescent personality: associations with Basal, awakening, and stress-induced cortisol responses.

    Science.gov (United States)

    Laceulle, Odilia M; Nederhof, Esther; van Aken, Marcel A G; Ormel, Johan

    2015-06-01

    The purpose of the present study was to investigate the associations between personality facets and hypothalamic-pituitary-adrenal (HPA) axis functioning. Previous studies have mainly focussed on stress-induced HPA-axis activation. We hypothesized that other characteristics of HPA-axis functioning would have a stronger association with personality based on the neuroendocrine literature. Data (n = 343) were used from the TRacking Adolescents' Individual Lives Survey (TRAILS), a large prospective cohort study of Dutch adolescents. We studied the association between facets of Neuroticism, Extraversion, and Conscientiousness and basal cortisol, the cortisol awakening response (CAR), and four measures of stress-induced HPA-axis activity. Basal cortisol levels were related to facets of all three personality traits. The CAR and stress-induced cortisol were not related to personality. Possibly due to its more trait-like nature, basal cortisol seems more informative than stress-induced cortisol when investigating trait-like characteristics such as personality facets.

  6. High lightning activity in maritime clouds near Mexico

    Science.gov (United States)

    Kucienska, B.; Raga, G. B.; Romero-Centeno, R.

    2012-09-01

    Lightning activity detected by the World Wide Lightning Location Network (WWLLN) over oceanic regions adjacent to Mexico is often as high as that observed over the continent. In order to explore the possible causes of the observed high flash density over those regions, the relationships between lightning, rainfall, vertical hydrometeor profiles, latent heating, wind variability and aerosol optical depth are analyzed. The characteristics of lightning and precipitation over four oceanic zones adjacent to Mexican coastlines are contrasted against those over the continent. The number of flashes per rainfall over some coastal maritime regions is found to be higher than over the continent. The largest number of flashes per rainfall is observed during the biomass burning season. In addition, we compare two smaller areas of the Tropical Pacific Ocean: one located within the Inter-Tropical Convergence Zone and characterized by high rainfall and weak lightning activity and the other one influenced by a continental wind jet and characterized by high rainfall and strong lightning activity. During the rainy season, the monthly distribution of lightning within the region influenced by the continental wind jet is contrary to that of rainfall. Moreover, the monthly variability of lightning is very similar to the variability of the meridional wind component and it is also related to the variability of aerosol optical depth. The analysis suggests that the high lightning activity observed over coastal Pacific region is linked to the continental cloud condensation nuclei advected over the ocean. Analysis of daily observations indicates that the greatest lightning density is observed for moderate values of the aerosol optical depth, between 0.2 and 0.35.

  7. A simple and highly effective process for the preparation of activated carbons with high surface area

    Energy Technology Data Exchange (ETDEWEB)

    Li Ying, E-mail: liyingjlu@163.com [College of Chemistry, Jilin University, Changchun 130012 (China); Ding Xuefeng; Guo Yupeng; Wang Lili; Rong Chunguang; Qu Yuning; Ma Xiaoyu [College of Chemistry, Jilin University, Changchun 130012 (China); Wang Zichen, E-mail: wangzc@jlu.edu.cn [College of Chemistry, Jilin University, Changchun 130012 (China)

    2011-06-15

    Highlights: {yields} High surface area activated carbon can be prepared by rice husk H{sub 3}PO{sub 4} without pretreatment. {yields} The characteristics of the activated carbon were greatly influenced by post-processing method. {yields} The lower SiO{sub 2} content of the activated carbons, the higher pore volume the carbons had. {yields} Some silica in rice husk reacted with H{sub 3}PO{sub 4} to form SiP{sub 2}O{sub 7} which could be removed by post-process. - Abstract: Activated carbons with high surface area were prepared by phosphoric acid as activation agent and rice husks as precursors. It was found that the characteristics of the activated carbons were influenced not only by the preparation but also by the post-processing method. The high surface area of the activated carbons was prepared under the optimum condition (50% H{sub 3}PO{sub 4} with impregnation ratio of 5:1, activation temperature of 500 deg. C, activation time of 0.5 h, wash water temperature of 100 deg. C). SiO{sub 2} content could affect the surface area of activated carbons, either. The lower SiO{sub 2} content of the activated carbons, the higher pore volume the carbons had. The SiO{sub 2} content was 11.2% when used the optimum condition. The explanation was that silicon element in rice husks reacted with H{sub 3}PO{sub 4} to form silicon phosphate (SiP{sub 2}O{sub 7}), and it could be proved further by X-ray diffraction analysis, SiP{sub 2}O{sub 7} could be removed by post-process.

  8. 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.)

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

    Energy Technology Data Exchange (ETDEWEB)

    Schilling, D.; Multhoff, G. [Klinikum rechts der Isar der Technischen Univ. Muenchen (Germany). Dept. of Radiation Oncology; Helmholtz Center Munich, CCG - Innate Immunity in Tumor Biology, Munich (Germany). German Research Center for Environmental Health - Inst. of Pathology; Bayer, C.; Emmerich, K.; Molls, M.; Vaupel, P. [Klinikum rechts der Isar der Technischen Univ. Muenchen (Germany). Dept. of Radiation Oncology; Huber, R.M. [Klinikum der Univ. Muenchen (Germany). Dept. of Pneumology

    2012-04-15

    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.)

  10. Active Photonic crystal fibers for high power applications

    DEFF Research Database (Denmark)

    Olausson, Christina Bjarnal Thulin

    . This plays an important role in high power lasers and ampliers with respect to efficiency, packaging, and thermal handling. The third part of the work has involved developing tools for characterizing the mode quality and stability of large core bers. Stable, single-mode bers with larger cores are essential......The photonic crystal ber technology provides means to realize bers optimized for high power operation, due to the large single-mode cores and the unique design exibility of the microstructure. The work presented in this thesis focuses on improving the properties of active photonic crystal bers...... for high power ber lasers and ampliers, and on adding new functionality to the fibers - all with the purpose of pushing the technology towards high powers. The first part of the work has been to investigate photo darkening, the mitigation of which is crucial in the quest for higher powers. The work has...

  11. [Basal cell carcinoma of prostate: a report of three cases].

    Science.gov (United States)

    Liu, Z; Ma, L L; Zhang, S D; Lu, M; Tian, Y; He, Q; Jin, J

    2016-02-18

    To explore the clinical pathological characteristics and improve the recognition in the diagnosis and treatment of basal cell carcinoma (BCC) of prostate. Three cases of BCC of prostate were reported and the relevant literature was reviewed to investigate the diagnosis and treatment of this disease. We analyzed three cases of prostatic BCC. Their ages were within a range of 57 to 83 years. One of them complained of hematuria and two complained of dysuria. All of them presented with prostatic hyperplasia. Two of them presented with high prostate specific antigen (PSA) and one with normal PSA. Case 1 had prostate cancer invasion of bladder, rectal fascia, with lymph node metastasis, bone metastasis and lung metastases. The patient received bladder resection+bilateral ureteral cutaneous ureterostomy+lymph node dissection on November 2, 2014 . Postoperative pathological diagnosis showed BCC. Reexamination of pelvic enhanced MRI in January 8, 2015 suggested pelvic recurrence. Abdominal enhanced CT showed multiple liver metastases and pancreatic metastasis on July 11, 2015. Prostate cancer specific death occurred in October 2015. Case 2 was diagnosed as BCC in prostate biopsy on March 27, 2015. Positron emission tomography and computed tomography (PET-CT) showed pulmonary metastasis and bone metastasis. Then the patient received chemotherapy, endocrine therapy and local radiation therapy. Reexamination of PET-CT on January 11, 2016 showed that the lung metastase tumors and bone metastase tumors were larger than before. Up to January 10, 2016, the patient was still alive. Postoperative pathological changes of transurethral resection of prostate (TURP) in case 3 showed BCC might be considered. The PET-CT suggested residual prostate cancer, which might be associated with bilateral pelvic lymph node metastasis. In April 20, 2016, the review of PET-CT showed pelvic huge irregular hybrid density shadow, about 14.5 cm×10.0 cm×12.9 cm in size, and tumor recurrence was

  12. Preclinical Study for Application of Fabricated High Activity Ir-192

    Energy Technology Data Exchange (ETDEWEB)

    Chun, Mi Son; Kang, Seung Hee; Oh, Young Taek; Jeong, Chul; Kim, Mi Hwa; Hwang, Jeong Hye; Kim, Hee Seong; Im, Eun Jeong [Ajou University, Suwon (Korea, Republic of)

    2005-10-15

    This study was performed to evaluate the feasibility and safety of high activity Ir-192 sources manufactured by KAERI(Korea Atomic Energy Research Institute) for application to present equipment such as various applicators inserted to patients and PLATO(Nucletron, Netherland) of treatment planning system and to evaluate safety and accuracy of Ir-192 as practical clinic use through in vitro dosimetry of Ir-192. We confirmed the physical and radiobiological safety of KAERI sources to use practical. KAERI sources are applicable to commercial high dose rate brachytherapy machine safely. Then those can be substituted for the imported sources such as sources made by Nucletron, Gammamed and exported to the foreign country

  13. Activated blended cement containing high volume coal fly ash

    Energy Technology Data Exchange (ETDEWEB)

    Shi, C.J.; Qian, J.S. [CJS Technology Inc., Burlington, ON (Canada)

    2001-10-01

    This study investigated the strength and equilibrium water extraction of blended cement containing high volume coal fly ash and activator CaCl{sub 2}. The addition of CaCl{sub 2} increased the strength of cement very significantly. Equilibrium water extraction indicated that the addition of CaCl{sub 2} decreased the pH of the pore solution, but accelerated the pozzolanic reactions between coal fly ash and lime, which became more obvious when the volume of fly ash in the cement was increased from 50-70%. Results from both strength and water extraction testing could conclude that CaCl{sub 2} is a good activator for the activation of pozzolanic reactivity of fly ash and for the improvement of early properties of fly ash cement and concrete.

  14. Basal Cell Nevus Syndrome. A Case Presentation

    Directory of Open Access Journals (Sweden)

    Ángel Luis Cruz Leiva

    2007-12-01

    Full Text Available Basal Cell Nevus Syndrome is an infrequent entity of very low incidence according to reports in medical literature. It is characterized by considerable groups of alterations which are presented in the organism in a variable way, and with localized lesions in the maxillofacial area. A 61 year-old white male patient who lives in the urban area of Cienfuegos city is presented. He has family references of numerous physical deformities since he was born such as mental retardation, presence of moles since the first decade of his life and augmentation of the mandibular body volume. The diagnosis was keratocysts based on the clinical and radiological examinations as well as histopathological studies.

  15. NEWBORNS OF HIGH RISK GROUPS AND ELECTROPHYSIOLOGICAL CARDIAC ACTIVITY DURING THE PERIOD OF EARLY ADAPTATION

    Directory of Open Access Journals (Sweden)

    T. S. Tumaeva

    2014-01-01

    Full Text Available Aim: to study characteristics of electrophysiological cardiac activity in children of risk groups and to assess possibilities of Holter-electrocardiography (H-ECG in revealing of cardiac dysfunction during the period of early adaptation. Patients and methods: 250 newborns were examined. The main group consisted of 200 children with cerebral ischemia (CI. This group was divided into 2 subgroups: 100 full-term and 100 premature (at various gestation age infants. Control group contained 50 children born at 38–40th weeks of gestation with physiological course of pregnancy and delivery, APGAR score of 8–9 points. Complex examination included H-ECG according the standard technic with evaluation of the hearth rate (HR during sleep and wakefulness; HRmin, HRmax; arrhythmias, conductivity disorders, duration of the intervals; rhythm variability. Results: according to the ECG children with CI, especially premature ones, and children delivered via Cesarean section more often had ST-T disturbances, arrhythmias (sinus tachycardia, less often — sinus bradycardia and conductivity disorders, Q-Tc prolongation. H-EGC revealed decrease of sleep HR, HRmin and HRmax in children with CI especially in delivered via Cesarean section. The most common arrhythmia was supraventricular extrasystole.  Pauses in rhythms and variability were the highest in premature children delivered via Cesarean section. Conclusions: hypoxia/ischemia is a trigger for development of cardiovascular dysfuncion in newborns. Premature and children delivered via Cesarean section form a group of high risk. H-ECG widens possibilities of revealing of symptoms of cardiac dysfunction (disturbances at the basal level of functioning, of adaptation resources of the sinus node, electric instability of the myocardium and heart rate variability in children of risk group for development of cardiovascular disorders. 

  16. Basal-Like Phenotype in a Breast Carcinoma Case Series from Sudan: Prevalence and Clinical/Pathological Correlations

    Directory of Open Access Journals (Sweden)

    Khalid Dafaallah Awadelkarim

    2011-01-01

    Full Text Available Basal-like breast cancer, an aggressive subtype associated with high grade, poor prognosis, and younger age, is reported frequently in Africa. We analyzed the expression of the basal cytokeratins (CKs 5/6 and 17 in a case series from Central Sudan and investigated correlations among basal CK status, ER, PgR, and Her-2/neu, and individual/clinicopathological data. Of 113 primary breast cancers 26 (23%, 38 (34%, and 46 (41% were, respectively, positive for CK5/6, CK17, and combined basal CKs (CK5/6 and/or CK17. Combined basal CK+ status was associated with higher grade (P<.03 and inversely correlated with ER (P<.002, PgR (P=.004 and combined ER and/or PgR (P<.0002. Two clusters based on all tested markers were generated by hierarchical cluster analysis and k-mean clustering: I: designated ``hormone receptors positive/luminal-like’’ and II: designated ``hormone receptors negative’’, including both basal-like and Her-2/neu+ tumors. The most important factors for dataset variance were ER status, followed by PgR, CK17, and CK5/6 statuses. Overall basal CKs were expressed in a fraction of cases comparable to that reported for East and West African case series. Lack of associations with age and tumor size may represent a special feature of basal-like breast cancer in Sudan.

  17. Yeast genetic analysis reveals the involvement of chromatin reassembly factors in repressing HIV-1 basal transcription.

    Directory of Open Access Journals (Sweden)

    Manuela Vanti

    2009-01-01

    Full Text Available Rebound of HIV viremia after interruption of anti-retroviral therapy is due to the small population of CD4+ T cells that remain latently infected. HIV-1 transcription is the main process controlling post-integration latency. Regulation of HIV-1 transcription takes place at both initiation and elongation levels. Pausing of RNA polymerase II at the 5' end of HIV-1 transcribed region (5'HIV-TR, which is immediately downstream of the transcription start site, plays an important role in the regulation of viral expression. The activation of HIV-1 transcription correlates with the rearrangement of a positioned nucleosome located at this region. These two facts suggest that the 5'HIV-TR contributes to inhibit basal transcription of those HIV-1 proviruses that remain latently inactive. However, little is known about the cell elements mediating the repressive role of the 5'HIV-TR. We performed a genetic analysis of this phenomenon in Saccharomyces cerevisiae after reconstructing a minimal HIV-1 transcriptional system in this yeast. Unexpectedly, we found that the critical role played by the 5'HIV-TR in maintaining low levels of basal transcription in yeast is mediated by FACT, Spt6, and Chd1, proteins so far associated with chromatin assembly and disassembly during ongoing transcription. We confirmed that this group of factors plays a role in HIV-1 postintegration latency in human cells by depleting the corresponding human orthologs with shRNAs, both in HIV latently infected cell populations and in particular single-integration clones, including a latent clone with a provirus integrated in a highly transcribed gene. Our results indicate that chromatin reassembly factors participate in the establishment of the equilibrium between activation and repression of HIV-1 when it integrates into the human genome, and they open the possibility of considering these factors as therapeutic targets of HIV-1 latency.

  18. Accelerator Production and Separations for High Specific Activity Rhenium-186

    Energy Technology Data Exchange (ETDEWEB)

    Jurisson, Silvia S. [Univ. of Missouri, Columbia, MO (United States); Wilbur, D. Scott [Univ. of Washington, Seattle, WA (United States)

    2016-04-01

    Tungsten and osmium targets were evaluated for the production of high specific activity rhenium-186. Rhenium-186 has potential applications in radiotherapy for the treatment of a variety of diseases, including targeting with monoclonal antibodies and peptides. Methods were evaluated using tungsten metal, tungsten dioxide, tungsten disulfide and osmium disulfide. Separation of the rhenium-186 produced and recycling of the enriched tungsten-186 and osmium-189 enriched targets were developed.

  19. Basal body temperature recordings in spontaneous abortion.

    Science.gov (United States)

    Cohen, J; Iffy, L; Keyser, H H

    1976-01-01

    Basal body temperature (BBT) charts taken during the cycle of conception in cases that resulted in spontaneous abortion appear to provide the best available information concerning events associated with time of fertilization in doomed gestations. This study is based on a series of 227 patients who had early spontaneous abortion occurring between January 1967 and December 1974. A diagnosis of pregnancy initiated regular assays of urinary estrogen and pregnanediol excretion. Patients were instructed to report any bleeding episode which might occur, and to preserve all tissues that might be expelled. A total of 11 basal body temperature charts were obtained from patients who had subsequent early spontaneous abortion. Chromosome studies and histologic investigations were conducted. Another group of 11 consecutive BBT records were obtained from patients who had normal deliveries. The study shows that women with normal cycles experience a midcycle temperature rise requiring 1 to 3 days. In subsequent patients, this time limit was exceeded in 7 out of 11 cases of early abortion, and in 4 of 11 fertilization that resulted in an apparently normal gestation and infant. As temperature rise resulted from vigorous progesterone secretion by the corpus luteum, subnormal levels indicate inadequate steroidogenesis in the early luteal phase, and falling estrogen and progesterone levels predicted fetal demise in all cases. These findings are useful in the management of early pregnancy that follows repeated spontaneous first trimester abortions or a prolonged period of infertility. They also confirm experimental and clinical evidence regarding the role of ovulation defects in the occurrence of various types of reproductive wastage, including early abortion, anatomic and chromosome defects of the embryo and others. Prospective studies of cycles of conception through BBT recordings/hormone assays may shed light in the understanding of defects of human reproduction.

  20. Mining Chemical Activity Status from High-Throughput Screening Assays

    KAUST Repository

    Soufan, Othman

    2015-12-14

    High-throughput screening (HTS) experiments provide a valuable resource that reports biological activity of numerous chemical compounds relative to their molecular targets. Building computational models that accurately predict such activity status (active vs. inactive) in specific assays is a challenging task given the large volume of data and frequently small proportion of active compounds relative to the inactive ones. We developed a method, DRAMOTE, to predict activity status of chemical compounds in HTP activity assays. For a class of HTP assays, our method achieves considerably better results than the current state-of-the-art-solutions. We achieved this by modification of a minority oversampling technique. To demonstrate that DRAMOTE is performing better than the other methods, we performed a comprehensive comparison analysis with several other methods and evaluated them on data from 11 PubChem assays through 1,350 experiments that involved approximately 500,000 interactions between chemicals and their target proteins. As an example of potential use, we applied DRAMOTE to develop robust models for predicting FDA approved drugs that have high probability to interact with the thyroid stimulating hormone receptor (TSHR) in humans. Our findings are further partially and indirectly supported by 3D docking results and literature information. The results based on approximately 500,000 interactions suggest that DRAMOTE has performed the best and that it can be used for developing robust virtual screening models. The datasets and implementation of all solutions are available as a MATLAB toolbox online at www.cbrc.kaust.edu.sa/dramote and can be found on Figshare.

  1. Mining Chemical Activity Status from High-Throughput Screening Assays.

    Directory of Open Access Journals (Sweden)

    Othman Soufan

    Full Text Available High-throughput screening (HTS experiments provide a valuable resource that reports biological activity of numerous chemical compounds relative to their molecular targets. Building computational models that accurately predict such activity status (active vs. inactive in specific assays is a challenging task given the large volume of data and frequently small proportion of active compounds relative to the inactive ones. We developed a method, DRAMOTE, to predict activity status of chemical compounds in HTP activity assays. For a class of HTP assays, our method achieves considerably better results than the current state-of-the-art-solutions. We achieved this by modification of a minority oversampling technique. To demonstrate that DRAMOTE is performing better than the other methods, we performed a comprehensive comparison analysis with several other methods and evaluated them on data from 11 PubChem assays through 1,350 experiments that involved approximately 500,000 interactions between chemicals and their target proteins. As an example of potential use, we applied DRAMOTE to develop robust models for predicting FDA approved drugs that have high probability to interact with the thyroid stimulating hormone receptor (TSHR in humans. Our findings are further partially and indirectly supported by 3D docking results and literature information. The results based on approximately 500,000 interactions suggest that DRAMOTE has performed the best and that it can be used for developing robust virtual screening models. The datasets and implementation of all solutions are available as a MATLAB toolbox online at www.cbrc.kaust.edu.sa/dramote and can be found on Figshare.

  2. Mining Chemical Activity Status from High-Throughput Screening Assays.

    Science.gov (United States)

    Soufan, Othman; Ba-alawi, Wail; Afeef, Moataz; Essack, Magbubah; Rodionov, Valentin; Kalnis, Panos; Bajic, Vladimir B

    2015-01-01

    High-throughput screening (HTS) experiments provide a valuable resource that reports biological activity of numerous chemical compounds relative to their molecular targets. Building computational models that accurately predict such activity status (active vs. inactive) in specific assays is a challenging task given the large volume of data and frequently small proportion of active compounds relative to the inactive ones. We developed a method, DRAMOTE, to predict activity status of chemical compounds in HTP activity assays. For a class of HTP assays, our method achieves considerably better results than the current state-of-the-art-solutions. We achieved this by modification of a minority oversampling technique. To demonstrate that DRAMOTE is performing better than the other methods, we performed a comprehensive comparison analysis with several other methods and evaluated them on data from 11 PubChem assays through 1,350 experiments that involved approximately 500,000 interactions between chemicals and their target proteins. As an example of potential use, we applied DRAMOTE to develop robust models for predicting FDA approved drugs that have high probability to interact with the thyroid stimulating hormone receptor (TSHR) in humans. Our findings are further partially and indirectly supported by 3D docking results and literature information. The results based on approximately 500,000 interactions suggest that DRAMOTE has performed the best and that it can be used for developing robust virtual screening models. The datasets and implementation of all solutions are available as a MATLAB toolbox online at www.cbrc.kaust.edu.sa/dramote and can be found on Figshare.

  3. Prolactin-induced prostate tumorigenesis links sustained Stat5 signaling with the amplification of basal/stem cells and emergence of putative luminal progenitors.

    Science.gov (United States)

    Sackmann-Sala, Lucila; Chiche, Aurélie; Mosquera-Garrote, Nerea; Boutillon, Florence; Cordier, Corinne; Pourmir, Ivan; Pascual-Mathey, Luz; Kessal, Karima; Pigat, Natascha; Camparo, Philippe; Goffin, Vincent

    2014-11-01

    Current androgen ablation therapies for prostate cancer are initially successful, but the frequent development of castration resistance urges the generation of alternative therapies and represents an important health concern. Prolactin/signal transducer and activator of transcription 5 (STAT5) signaling is emerging as a putative target for alternative treatment for prostate cancer. However, mechanistic data for its role in development or progression of prostate tumors are scarce. In vivo mouse studies found that local prolactin induced the amplification of prostate epithelial basal/stem cells. Because these cells are proposed cells of origin for prostate cancer and disease recurrence, we looked further into this amplification. Our results indicated that sustained Stat5 activation was associated with the occurrence of abnormal basal/stem cell clusters in prostate epithelium of prostate-specific prolactin-transgenic mice. Analysis of epithelial areas containing these clusters found high proliferation, Stat5 activation, and expression of stem cell antigen 1. Furthermore, enhanced prolactin signaling also led to amplification of a luminal cell population that was positive for stem cell antigen 1. These cells may originate from amplified basal/stem cells and might represent important progenitors for tumor development in prostate epithelium. These data provide a deeper understanding of the initial stages of prostate tumorigenesis induced by prolactin to help determine whether this hormone or its downstream messengers could be useful targets for prostate cancer treatment in the future.

  4. Fibrinolytic changes in pregnant women on highly active antiretroviral therapy.

    Science.gov (United States)

    Osime, Odaburhine E; Ese-Onakewhor, Joseph U; Kolade, Samson O

    2015-02-01

    To report on the changes in fibrinolytic activity in human immunodeficiency virus (HIV) infected pregnant women who are undergoing highly active antiretroviral therapy (HAART). Blood was collected from 50 HIV positive women on HAART (test subjects), and 50 HIV positive women not on HAART (controls). These women were attending the prevention of mother to child clinic (PMTCT) of the University of Benin Teaching Hospital, Benin City, Nigeria from January to June 2014. Standard manual techniques were used to estimate plasma fibrinogen concentration (PFC), euglobulin lysis time (ELT), packed cell volume (PCV), and plasma viscosity (PV). The mean ± standard error of mean (SEM) of PFC was 4.02±0.13 g/l and ELT from the test subjects was 378±15 mins was significantly higher (p0.05). There were differences in the various parameters investigated when the various trimesters were compared. These differences did not, however, follow a particular pattern. Highly active antiretroviral therapy can cause changes in fibrinolytic activity that may predispose pregnant women to hyperfibrinogenemia and anemia.

  5. High Electrocatalytic Hydrogen Evolution Activity of an Anomalous Ruthenium Catalyst

    KAUST Repository

    Zheng, Yao

    2016-11-28

    Hydrogen evolution reaction (HER) is a critical process due to its fundamental role in electrocatalysis. Practically, the development of high-performance electrocatalysts for HER in alkaline media is of great importance for the conversion of renewable energy to hydrogen fuel via photoelectrochemical water splitting. However, both mechanistic exploration and materials development for HER under alkaline conditions are very limited. Precious Pt metal, which still serves as the state-of-the-art catalyst for HER, is unable to guarantee a sustainable hydrogen supply. Here we report an anomalously structured Ru catalyst that shows 2.5 times higher hydrogen generation rate than Pt and is among the most active HER electrocatalysts yet reported in alkaline solutions. The identification of new face-centered cubic crystallographic structure of Ru nanoparticles was investigated by high-resolution transmission electron microscopy imaging, and its formation mechanism was revealed by spectroscopic characterization and theoretical analysis. For the first time, it is found that the Ru nanocatalyst showed a pronounced effect of the crystal structure on the electrocatalytic activity tested under different conditions. The combination of electrochemical reaction rate measurements and density functional theory computation shows that the high activity of anomalous Ru catalyst in alkaline solution originates from its suitable adsorption energies to some key reaction intermediates and reaction kinetics in the HER process.

  6. AHEAD: Integrated Activities in the High Energy Astrophysics Domain

    Science.gov (United States)

    Piro, Luigi; Natalucci, Lorenzo; Ahead Consortium

    2015-09-01

    AHEAD (Integrated Activities in the High Energy Astrophysics Domain) is a forthcoming project approved in the framework of the European Horizon 2020 program (Research Infrastructures for High Energy Astrophysics). The overall objective of AHEAD is to integrate national efforts in high-energy Astrophysics and to promote the domain at the European level, to keep its community at the cutting edge of science and technology and ensure that space observatories for high-energy astrophysics, with particular regard to Athena, are at the state of the art. AHEAD will integrate key research infrastructures for on-ground test and calibration of space-based sensors and electronics and promote their coordinated use. In parallel, the best facilities for data analysis of high-energy astrophysical observatories will be made available to the European community. The technological development will focus on the improvement of selected critical technologies, background modeling, cross calibration, and feasibility studies of space-based instrumentation for the benefit of future high energy missions like Athena, and the best exploitation of existing observatories. AHEAD will support the community via grants for collaborative studies, dissemination of results, and promotion of workshops. A strong public outreach package will ensure that the domain is well publicized at national, European and International level. Networking, joint research activities and access to infrastructures as devised in AHEAD, will serve to establish strong connections between institutes and industry to create the basis for a more rapid advancement of high-energy astrophysical science, space oriented instrumentation and cutting-edge sensor technology in Europe. This enables the development of new technologies and the associated growth of the European technology market with a dedicated technology innovation package, as well as the creation of a new generation of researchers.

  7. High Intrinsic Catalytic Activity of Two-Dimensional Boron Monolayers for Hydrogen Evolution Reaction

    CERN Document Server

    Shi, Li; Ouyang, Yixin; Wang, Jinlan

    2016-01-01

    Two-dimensional (2D) boron monolayers have been successfully synthesized on silver substrate very recently. Their potential application is thus of great significance. In this work, we explore the possibility of boron monolayers (BMs) as electrocatalysts for hydrogen evolution reaction (HER) by first-principle method. Our calculations show that the BMs are active catalysts for HER with nearly zero free energy of hydrogen adsorption, metallic conductivity and plenty of active sites in the basal plane. The effect of the substrate on the HER activity is further assessed. It is found that the substrate has a positive effect on the HER performance caused by the competitive effect of mismatch strain and charge transfer. The indepth understanding of the structure dependent HER activity is also provided.

  8. The SOX11 transcription factor is a critical regulator of basal-like breast cancer growth, invasion, and basal-like gene expression.

    Science.gov (United States)

    Shepherd, Jonathan H; Uray, Ivan P; Mazumdar, Abhijit; Tsimelzon, Anna; Savage, Michelle; Hilsenbeck, Susan G; Brown, Powel H

    2016-03-15

    Basal-like breast cancers (BLBCs) are aggressive breast cancers associated with poor survival. Defining the key drivers of BLBC growth will allow identification of molecules for targeted therapy. In this study, we performed a primary screen integrating multiple assays that compare transcription factor expression and activity in BLBC and non-BLBC at the RNA, DNA, and protein levels. This integrated screen identified 33 transcription factors that were elevated in BLBC in multiple assays comparing mRNA expression, DNA cis-element sequences, or protein DNA-binding activity. In a secondary screen to identify transcription factors critical for BLBC cell growth, 8 of the 33 candidate transcription factors (TFs) were found to be necessary for growth in at least two of three BLBC cell lines. Of these 8 transcription factors, SOX11 was the only transcription factor required for BLBC growth, but not for growth of non-BLBC cells. Our studies demonstrate that SOX11 is a critical regulator of multiple BLBC phenotypes, including growth, migration, invasion, and expression of signature BLBC genes. High SOX11 expression was also found to be an independent prognostic indicator of poor survival in women with breast cancer. These results identify SOX11 as a potential target for the treatment of BLBC, the most aggressive form of breast cancer.

  9. High Sulfation and a High Molecular Weight Are Important for Anti-hepcidin Activity of Heparin

    Science.gov (United States)

    Asperti, Michela; Naggi, Annamaria; Esposito, Emiliano; Ruzzenenti, Paola; Di Somma, Margherita; Gryzik, Magdalena; Arosio, Paolo; Poli, Maura

    2016-01-01

    Heparins are efficient inhibitors of hepcidin expression even in vivo, where they induce an increase of systemic iron availability. Heparins seem to act by interfering with BMP6 signaling pathways that control the expression of liver hepcidin, causing the suppression of SMAD1/5/8 phosphorylation. The anti-hepcidin activity persists also when the heparin anticoagulant property is abolished or reduced by chemical reactions of oxidation/reduction (glycol-split, Gs-Heparins) or by high sulfation (SS-Heparins), but the structural characteristics needed to optimize this inhibitory activity have not been studied in detail. To this aim we analyzed three different heparins (Mucosal Heparin, the Glycol split RO-82, the partially desulfated glycol-split RO-68 and the oversulfated SSLMWH) and separated them in fractions of molecular weight in the range 4–16 kD. Since the distribution of the negative charges in heparins contributes to the activity, we produced 2-O- and 6-O-desulfated heparins. These derivatives were analyzed for the capacity to inhibit hepcidin expression in hepatic HepG2 cells and in mice. The two approaches produced consistent results and showed that the anti-hepcidin activity strongly decreases with molecular weight below 7 kD, with high N-acetylation and after 2-O and 6-O desulfation. The high sulfation and high molecular weight properties for efficient anti-hepcidin activity suggest that heparin is involved in multiple binding sites. PMID:26955355

  10. Active beam integrator for high power coherent lasers

    Energy Technology Data Exchange (ETDEWEB)

    Laguarta, F.; Armengol, J.; Vega, F.; Lupon, N. [Univ. Politecnica de Catalunya, Terrassa (Spain). Dept. d`Optica i Optometria

    1996-12-31

    In laser materials processing applications it is often necessary to work with uniform intensity distributions. This goal is quite difficult to achieve when dealing with high power laser beams, and becomes critical for a successful application involving surface heat treatment of non-metallic materials. The authors have designed and tested a very simple beam shaper for transforming the initial intensity distribution of a CO{sub 2} laser beam mode into a more uniform intensity profile. The beam shaper is a two-faceted mirror for active integration of high power coherent laser beams. After reflection in the faceted mirror, a TEM00 or TEM01 CO{sub 2} laser beam is divided into two beamlets that overlap to give a more uniform intensity distribution. A sharp interference pattern due to the high spatial coherence of the incident beam appears. This interference pattern is actively integrated by a high-frequency longitudinal displacement of one of the facets. This provides a change in the relative phase of the two beamlets, and consequently the interference pattern vibrates and its contribution to the intensity distribution averages out. When sweeping this distribution over a sample, a uniform amount of energy is deposited at every point of its surface. It must be emphasized that unlike multifaceted mirrors, the two-facet integrator may provide uniform intensity profiles over any working distance. Finally, as in other integration devices an imaging system may be used to obtain a spot of the shape and the size desired for a particular application.

  11. Microbial fuel cells with highly active aerobic biocathodes

    Science.gov (United States)

    Milner, Edward M.; Popescu, Dorin; Curtis, Tom; Head, Ian M.; Scott, Keith; Yu, Eileen H.

    2016-08-01

    Microbial fuel cells (MFCs), which convert organic waste to electricity, could be used to make the wastewater infrastructure more energy efficient and sustainable. However, platinum and other non-platinum chemical catalysts used for the oxygen reduction reaction (ORR) at the cathode of MFCs are unsustainable due to their high cost and long-term degradation. Aerobic biocathodes, which use microorganisms as the biocatalysts for cathode ORR, are a good alternative to chemical catalysts. In the current work, high-performing aerobic biocathodes with an onset potential for the ORR of +0.4 V vs. Ag/AgCl were enriched from activated sludge in electrochemical half-cells poised at -0.1 and + 0.2 V vs. Ag/AgCl. Gammaproteobacteria, distantly related to any known cultivated gammaproteobacterial lineage, were identified as dominant in these working electrode biofilms (23.3-44.3% of reads in 16S rRNA gene Ion Torrent libraries), and were in very low abundance in non-polarised control working electrode biofilms (0.5-0.7%). These Gammaproteobacteria were therefore most likely responsible for the high activity of biologically catalysed ORR. In MFC tests, a high-performing aerobic biocathode increased peak power 9-fold from 7 to 62 μW cm-2 in comparison to an unmodified carbon cathode, which was similar to peak power with a platinum-doped cathode at 70 μW cm-2.

  12. Genomic analysis of smoothened inhibitor resistance in basal cell carcinoma.

    Science.gov (United States)

    Sharpe, Hayley J; Pau, Gregoire; Dijkgraaf, Gerrit J; Basset-Seguin, Nicole; Modrusan, Zora; Januario, Thomas; Tsui, Vickie; Durham, Alison B; Dlugosz, Andrzej A; Haverty, Peter M; Bourgon, Richard; Tang, Jean Y; Sarin, Kavita Y; Dirix, Luc; Fisher, David C; Rudin, Charles M; Sofen, Howard; Migden, Michael R; Yauch, Robert L; de Sauvage, Frederic J

    2015-03-09

    Smoothened (SMO) inhibitors are under clinical investigation for the treatment of several cancers. Vismodegib is approved for the treatment of locally advanced and metastatic basal cell carcinoma (BCC). Most BCC patients experience significant clinical benefit on vismodegib, but some develop resistance. Genomic analysis of tumor biopsies revealed that vismodegib resistance is associated with Hedgehog (Hh) pathway reactivation, predominantly through mutation of the drug target SMO and to a lesser extent through concurrent copy number changes in SUFU and GLI2. SMO mutations either directly impaired drug binding or activated SMO to varying levels. Furthermore, we found evidence for intra-tumor heterogeneity, suggesting that a combination of therapies targeting components at multiple levels of the Hh pathway is required to overcome resistance.

  13. Highly porous activated carbons prepared from carbon rich Mongolian anthracite by direct NaOH activation

    Science.gov (United States)

    Byamba-Ochir, Narandalai; Shim, Wang Geun; Balathanigaimani, M. S.; Moon, Hee

    2016-08-01

    Highly porous activated carbons (ACs) were prepared from Mongolian raw anthracite (MRA) using sodium hydroxide as an activation agent by varying the mass ratio (powdered MRA/NaOH) as well as the mixing method of chemical agent and powdered MRA. The specific BET surface area and total pore volume of the prepared MRA-based activated carbons (MACs) are in the range of 816-2063 m2/g and of 0.55-1.61 cm3/g, respectively. The pore size distribution of MACs show that most of the pores are in the range from large micropores to small mesopores and their distribution can be controlled by the mass ratio and mixing method of the activating agent. As expected from the intrinsic property of the MRA, the highly graphitic surface morphology of prepared carbons was confirmed from Raman spectra and transmission electron microscopy (TEM) studies. Furthermore the FTIR and XPS results reveal that the preparation of MACs with hydrophobic in nature is highly possible by controlling the mixing conditions of activating agent and powdered MRA. Based on all the results, it is suggested that the prepared MACs could be used for many specific applications, requiring high surface area, optimal pore size distribution, proper surface hydrophobicity as well as strong physical strength.

  14. mRNA Noise Reveals that Activators Induce a Biphasic Response in the Promoter Kinetics of Highly Regulated Genes

    Science.gov (United States)

    Quinn, Katie; To, Tsz-Leung; Maheshri, Narendra

    2012-02-01

    A dominant source of fluctuations in gene expression is thought to be the process of transcription. The statistics of these fluctuations arise from the kinetics of transcription. Multiple studies suggest the bulk of fluctuations can be understood by a simple process where genes are inactive for exponentially distributed times punctuated by geometric bursts of mRNA. Yet it's largely unknown how cis and trans factors affect the two lumped kinetic parameters, burst size and burst frequency, that describe this process. Importantly, how these parameters are regulated in a single gene can qualitatively affect the dynamical behavior of the network it is embedded within. Here, we ask whether transcriptional activators increase gene expression by increasing the burst size or burst frequency. We do so by deducing these parameters from steady-state mRNA distributions measured in individual yeast cells using single molecule mRNA FISH. We find that for both a synthetic and natural promoter, activators appear to first increase burst size, then burst frequency. We suggest this biphasic response may be common to all highly regulated genes and was previously unappreciated because of measurement techniques. Furthermore, its origins appear to relate to cis events at the promoter, and may arise from combinations of basal and activator-dependent bursts. Our measurements shed new light on transcriptional mechanisms and should assist in building synthetic promoters with tunable statistics.

  15. Active Change in Psychodynamic Therapy: Moments of High Receptiveness.

    Science.gov (United States)

    De Gauna, Mariano De Iceta Ibáñez; Roibal, M Angela Soler; Ruiz, José Antonio Méndez; Fernández, Joaquin Ingelmo; Bleichmar, Hugo B

    2015-01-01

    This article presents the concept of "moments of high receptiveness" (MoHR or "Momentos de Alta Receptividad"), which is derived from the concept of "experiential coupling" ("Acoplamiento de Experiencias") proposed by Bleichmar (2001). Experiential coupling recently received empirical support by the work of Schiller and colleagues (2010). We will also show the conceptual placing of moments of high receptiveness with respect to the developments of Stern and colleagues (Stern and et al., 1998; Stern, 2004). In order to achieve both objectives, we focus on various clinical vignettes stressing the differences in repercussions of the technique. We describe use of stimuli for active evocation, explain how to identify moments of high receptiveness, and review ways to take advantage of these moments. Lastly, to minimize the risk of iatrogenic symptoms, we examine the role of therapists and some features of the therapeutic process when using this technique.

  16. Abnormal Basal Ganglia Functional Connectivity in Idiopathic Generalized Epilepsy

    Institute of Scientific and Technical Information of China (English)

    Cheng Luo; Yang Xia; Zhi-Wei Guo; Dong Zhou

    2011-01-01

    The basal ganglia have been implicated in a modulation role in idiopathic generalized epilepsy (IGE) by an invasive electrophysioigic means.This paper investigates the basal ganglia functional connectivity by using the region-wise functional connection analysis in resting-state functional magnetic resonance imaging (fMRi) in IGE.The increased functional connectivity within basal ganglia,and between the basal ganglia and the thalamus,and decreased functional connectivity between basal ganglia and motor cortex are found in IGE compared with the controls. These findings not only implicate dysfunctional integration in the motor loop in IGE and the enhanced interaction in the modulated loop,but also suggest that the basal ganglia modulate the generalized epileptic discharges with the influence over thalamus in the corticothalamus network.

  17. Telomerase activation by genomic rearrangements in high-risk neuroblastoma.

    Science.gov (United States)

    Peifer, Martin; Hertwig, Falk; Roels, Frederik; Dreidax, Daniel; Gartlgruber, Moritz; Menon, Roopika; Krämer, Andrea; Roncaioli, Justin L; Sand, Frederik; Heuckmann, Johannes M; Ikram, Fakhera; Schmidt, Rene; Ackermann, Sandra; Engesser, Anne; Kahlert, Yvonne; Vogel, Wenzel; Altmüller, Janine; Nürnberg, Peter; Thierry-Mieg, Jean; Thierry-Mieg, Danielle; Mariappan, Aruljothi; Heynck, Stefanie; Mariotti, Erika; Henrich, Kai-Oliver; Gloeckner, Christian; Bosco, Graziella; Leuschner, Ivo; Schweiger, Michal R; Savelyeva, Larissa; Watkins, Simon C; Shao, Chunxuan; Bell, Emma; Höfer, Thomas; Achter, Viktor; Lang, Ulrich; Theissen, Jessica; Volland, Ruth; Saadati, Maral; Eggert, Angelika; de Wilde, Bram; Berthold, Frank; Peng, Zhiyu; Zhao, Chen; Shi, Leming; Ortmann, Monika; Büttner, Reinhard; Perner, Sven; Hero, Barbara; Schramm, Alexander; Schulte, Johannes H; Herrmann, Carl; O'Sullivan, Roderick J; Westermann, Frank; Thomas, Roman K; Fischer, Matthias

    2015-10-29

    Neuroblastoma is a malignant paediatric tumour of the sympathetic nervous system. Roughly half of these tumours regress spontaneously or are cured by limited therapy. By contrast, high-risk neuroblastomas have an unfavourable clinical course despite intensive multimodal treatment, and their molecular basis has remained largely elusive. Here we have performed whole-genome sequencing of 56 neuroblastomas (high-risk, n = 39; low-risk, n = 17) and discovered recurrent genomic rearrangements affecting a chromosomal region at 5p15.33 proximal of the telomerase reverse transcriptase gene (TERT). These rearrangements occurred only in high-risk neuroblastomas (12/39, 31%) in a mutually exclusive fashion with MYCN amplifications and ATRX mutations, which are known genetic events in this tumour type. In an extended case series (n = 217), TERT rearrangements defined a subgroup of high-risk tumours with particularly poor outcome. Despite a large structural diversity of these rearrangements, they all induced massive transcriptional upregulation of TERT. In the remaining high-risk tumours, TERT expression was also elevated in MYCN-amplified tumours, whereas alternative lengthening of telomeres was present in neuroblastomas without TERT or MYCN alterations, suggesting that telomere lengthening represents a central mechanism defining this subtype. The 5p15.33 rearrangements juxtapose the TERT coding sequence to strong enhancer elements, resulting in massive chromatin remodelling and DNA methylation of the affected region. Supporting a functional role of TERT, neuroblastoma cell lines bearing rearrangements or amplified MYCN exhibited both upregulated TERT expression and enzymatic telomerase activity. In summary, our findings show that remodelling of the genomic context abrogates transcriptional silencing of TERT in high-risk neuroblastoma and places telomerase activation in the centre of transformation in a large fraction of these tumours.

  18. Passive and Active Monitoring on a High Performance Research Network.

    Energy Technology Data Exchange (ETDEWEB)

    Matthews, Warren

    2001-05-01

    The bold network challenges described in ''Internet End-to-end Performance Monitoring for the High Energy and Nuclear Physics Community'' presented at PAM 2000 have been tackled by the intrepid administrators and engineers providing the network services. After less than a year, the BaBar collaboration has collected almost 100 million particle collision events in a database approaching 165TB (Tera=10{sup 12}). Around 20TB has been exported via the Internet to the BaBar regional center at IN2P3 in Lyon, France, for processing and around 40 TB of simulated events have been imported to SLAC from Lawrence Livermore National Laboratory (LLNL). An unforseen challenge has arisen due to recent events and highlighted security concerns at DoE funded labs. New rules and regulations suggest it is only a matter of time before many active performance measurements may not be possible between many sites. Yet, at the same time, the importance of understanding every aspect of the network and eradicating packet loss for high throughput data transfers has become apparent. Work at SLAC to employ passive monitoring using netflow and OC3MON is underway and techniques to supplement and possibly replace the active measurements are being considered. This paper will detail the special needs and traffic characterization of a remarkable research project, and how the networking hurdles have been resolved (or not!) to achieve the required high data throughput. Results from active and passive measurements will be compared, and methods for achieving high throughput and the effect on the network will be assessed along with tools that directly measure throughput and applications used to actually transfer data.

  19. Reelin signaling in the basal ganglia: comparative neuroanatomy and implications for vocal behavior

    OpenAIRE

    Fraley, Elizabeth Ross

    2017-01-01

    Vocal learning is a complex motor activity that relies on the coordination of different brain regions including the basal ganglia. By studying the vocal learning zebra finch, this work has uncovered a novel pathway that is regulated by singing behavior. The Reelin-signaling pathway like the human language transcription factor, FoxP2, is regulated in a basal ganglia region, Area X. The pathway was found to be regulated during the sensorimotor phase of song learning in finches as well as in adu...

  20. Hedgehog pathway inhibition in advanced basal cell carcinoma: latest evidence and clinical usefulness

    Science.gov (United States)

    Silapunt, Sirunya; Chen, Leon; Migden, Michael R.

    2016-01-01

    Treatment of locally advanced basal cell carcinomas (laBCCs) with large, aggressive, destructive, and disfiguring tumors, or metastatic disease is challenging. Dysregulation of the Hedgehog (Hh) signaling pathway has been identified in the vast majority of basal cell carcinomas (BCCs). There are two United States Food and Drug Administration (US FDA)-approved Hh pathway inhibitors (HPIs) that exhibit antitumor activity in advanced BCC with an acceptable safety profile. Common adverse effects include muscle spasms, dysgeusia, alopecia, fatigue, nausea and weight loss. PMID:27583029

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

    NARCIS (Netherlands)

    Ricklefs, RE; Konarzewski, M; Daan, S

    1996-01-01

    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''

  2. 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''

  3. Plant basal resistance: genetics, biochemistry, and impacts on plant-biotic interactions

    NARCIS (Netherlands)

    Ahmad, S.

    2012-01-01

    Basal resistance depends largely on a diverse range of defence mechanisms that become active upon attack by pathogens or insects. These mechanisms range from rapid stomatal closure and production of reactive oxygen species, to callose deposition and defence gene induction. It is commonly assumed tha

  4. High Performance Activity Practices in Small Firms in Romania

    Directory of Open Access Journals (Sweden)

    Gabriela ŢUŢUEANU

    2014-12-01

    Full Text Available High Performance Activity Practices in Small Firms in Romania Abstract: High performance activity practices (HPAPs are human resource management activities aimed at stimulating employee and organisational performance. The application of HPAPs is not widespread in small organisations. We examine whether the implementation of coherent bundles of HPAPs (aimed at employee ability, employee motivation or at the opportunity to perform depends on the scarcity of resources, as reflected in the size of the company, and on strategic decision-making in small firms related to the owner’s expertise and attitudes. In our research, a total of 224 employees from 50 small organisations were asked to rate the presence of HPAPs in their organisation. These averaged perceptions were linked to information provided by the owner–managers on the size of their firm and their own expertise and attitudes. The findings support that smaller but coherent bundles of HPAPs can be found in small organisations and that the implementation of these bundles depends on available resources, strategic decision-making and the combination of the two. These findings highlight the need to integrate the notions of resource poverty and strategic decision-making to understand the uptake of bundles of HPAPs within small firms.

  5. Lichen planopilaris after imiquimod 5% cream for multiple BCC in basal cell naevus syndrome.

    Science.gov (United States)

    Drummond, Alessandra; Pichler, Janine; Argenziano, Giuseppe; Zalaudek, Iris; Longo, Caterina; Lallas, Aimilios; Piana, Simonetta; Moscarella, Elvira

    2015-11-01

    Basal cell naevus syndrome is an inherited autosomal dominant genetic disorder characterised by multiple basal cell carcinomas (BCC), skeletal, neurological and opthalmological abnormalities. The treatment of choice of the often multiple and large BCC consists of a combined approach including surgery, liquid nitrogen and other topical treatment modalities. Imiquimod 5% cream is an immune-response-modifying drug with antiviral and anti-tumour activity. Recent reports have associated the immune-stimulant properties of imiquimod with the exacerbation of several autoimmune skin diseases, such as eczema, psoriasis, vitiligo and lichenoid dermatitis. Here we report a patient with basal cell naevus syndrome who developed a lichen planopilaris on the same site of the scalp, which had been previously treated with two cycles of imiquimod for multiple BCC.

  6. Human-specific gene ARHGAP11B promotes basal progenitor amplification and neocortex expansion.

    Science.gov (United States)

    Florio, Marta; Albert, Mareike; Taverna, Elena; Namba, Takashi; Brandl, Holger; Lewitus, Eric; Haffner, Christiane; Sykes, Alex; Wong, Fong Kuan; Peters, Jula; Guhr, Elaine; Klemroth, Sylvia; Prüfer, Kay; Kelso, Janet; Naumann, Ronald; Nüsslein, Ina; Dahl, Andreas; Lachmann, Robert; Pääbo, Svante; Huttner, Wieland B

    2015-03-27

    Evolutionary expansion of the human neocortex reflects increased amplification of basal progenitors in the subventricular zone, producing more neurons during fetal corticogenesis. In this work, we analyze the transcriptomes of distinct progenitor subpopulations isolated by a cell polarity-based approach from developing mouse and human neocortex. We identify 56 genes preferentially expressed in human apical and basal radial glia that lack mouse orthologs. Among these, ARHGAP11B has the highest degree of radial glia-specific expression. ARHGAP11B arose from partial duplication of ARHGAP11A (which encodes a Rho guanosine triphosphatase-activating protein) on the human lineage after separation from the chimpanzee lineage. Expression of ARHGAP11B in embryonic mouse neocortex promotes basal progenitor generation and self-renewal and can increase cortical plate area and induce gyrification. Hence, ARHGAP11B may have contributed to evolutionary expansion of human neocortex.

  7. Basal cell carcinoma in oculo-cutaneous albinism

    Directory of Open Access Journals (Sweden)

    Ajay Kumar

    2016-06-01

    Full Text Available The basal cell carcinoma is the most common skin tumour especially affecting the white individuals worldwide. The exact incidence of basal cell carcinoma is not known from India but non melanoma skin cancers comprises about 1-2% of cutaneous tumour in India. The most common skin tumour is squamous cell carcinoma in albinism and the incidence of basal cell carcinoma is less. Hereby, we report a peculiar case of basal cell carcinoma in albinism to highlights the importance of early recognition and diagnosis of suspected lesions by performing histopathological examination in unusual circumstances. [Int J Res Med Sci 2016; 4(6.000: 2452-2454

  8. Use of dominant harmonic active filters in high power applications

    Science.gov (United States)

    Cheng, Po-Tai

    The application of power electronics equipment is increasing rapidly. It is estimated that 60% of electrical power will be processed by power electronics equipment by year 2000. These equipments typically require rectifiers for AC-DC power conversion. Due to their nonlinear nature, most rectifiers draw harmonic current from the utility grid. The harmonic current causes higher energy losses, and may excite resonance conditions in the utility grid. Harmonic standards such as IEEE 519 and IEC 1000-3-2 have been proposed to regulate the harmonic current and voltage levels. This work is to develop a dominant harmonic active filter (DHAF) to realize a cost-effective active filtering solution for nonlinear loads in the range of megawatt and above. The DHAF system achieves harmonic isolation at dominant harmonic frequencies, e.g. the 5th and 7th. This approach allows use of low switching frequency and small rating active filter inverters (1%--2% of the load MVA rating) for implementation. Review of conventional passive filters and various active filters based on high bandwidth PWM inverters is provided. The control theory of the DHAF system is presented. Comparison of the DHAF system and other dominant harmonic filtering approach is provided. Simulation results and laboratory prototype test results are presented to validate the effectiveness of the proposed DHAF system.

  9. Significance of High-frequency Electrical Brain Activity.

    Science.gov (United States)

    Kobayashi, Katsuhiro; Akiyama, Tomoyuki; Agari, Takashi; Sasaki, Tatsuya; Shibata, Takashi; Hanaoka, Yoshiyuki; Akiyama, Mari; Endoh, Fumika; Oka, Makio; Date, Isao

    2017-06-01

     Electroencephalogram (EEG) data include broadband electrical brain activity ranging from infra-slow bands (frequency bands (e.g., the approx. 10 Hz alpha rhythm) to high-frequency bands of up to 500 Hz. High-frequency oscillations (HFOs) including ripple and fast ripple oscillations (80-200 Hz and>200 / 250 Hz, respectively) are particularly of note due to their very close relationship to epileptogenicity, with the possibility that they could function as a surrogate biomarker of epileptogenicity. In contrast, physiological high-frequency activity plays an important role in higher brain functions, and the differentiation between pathological / epileptic and physiological HFOs is a critical issue, especially in epilepsy surgery. HFOs were initially recorded with intracranial electrodes in patients with intractable epilepsy as part of a long-term invasive seizure monitoring study. However, fast oscillations (FOs) in the ripple and gamma bands (40-80 Hz) are now noninvasively detected by scalp EEG and magnetoencephalography, and thus the scope of studies on HFOs /FOs is rapidly expanding.

  10. Highly Active Rare-Earth-Metal La-Doped Photocatalysts: Fabrication, Characterization, and Their Photocatalytic Activity

    Directory of Open Access Journals (Sweden)

    S. Anandan

    2012-01-01

    Full Text Available Efficient La-doped TiO2 photocatalysts were prepared by sol-gel method and extensively characterized by various sophisticated techniques. The photocatalytic activity of La-doped TiO2 was evaluated for the degradation of monocrotophos (MCPs in aqueous solution. It showed higher rate of degradation than pure TiO2 for the light of wavelength of 254 nm and 365 nm. The rate constant of TiO2 increases with increasing La loading and exhibits maximum rate for 1% La loading. The photocatalytic activities of La-doped TiO2 are compared with La-doped ZnO; the reaction rate of the former is ~1.8 and 1.1 orders higher than the latter for the lights of wavelength 254 nm and 365 nm, respectively. The relative photonic efficiency of La-doped TiO2 is relatively higher than La-doped ZnO and commercial photocatalysts. Overall, La-doped TiO2 is the most active photocatalyst and shows high relative photonic efficiencies and high photocatalytic activity for the degradation of MCP. The enhanced photocatalytic activity of La-doped TiO2 is mainly due to the electron trapping by lanthanum metal ions, small particle size, large surface area, and high surface roughness of the photocatalysts.

  11. Sulfurized activated carbon for high energy density supercapacitors

    Science.gov (United States)

    Huang, Yunxia; Candelaria, Stephanie L.; Li, Yanwei; Li, Zhimin; Tian, Jianjun; Zhang, Lili; Cao, Guozhong

    2014-04-01

    Sulfurized activated carbon (SAC), made by coating the pore surface with thiophenic sulfur functional groups from the pyrolysis of sulfur flakes, were characterized and tested for supercapacitor applications. From X-ray photoelectron spectroscopy (XPS), the sulfur content in the SAC was found to be 2.7 at%. Electrochemical properties from potentiostatic and galvanostatic measurements, and electrochemical impedance spectroscopy (EIS) were used to evaluate the effect of sulfur on porous carbon electrodes. The SAC electrode exhibits better conductivity, and an obvious increase in specific capacitance that is almost 40% higher than plain activated carbons (ACs) electrode at a high current density of 1.4 A g-1. The proposed mechanism for improved conductivity and capacitive performance due to the sulfur functional groups on ACs will be discussed.

  12. Easy and Rapid Purification of Highly Active Nisin

    Directory of Open Access Journals (Sweden)

    André Abts

    2011-01-01

    Full Text Available Nisin is an antimicrobial peptide produced and secreted by several L. lactis strains and is specifically active against Gram-positive bacteria. In previous studies, nisin was purified via cation exchange chromatography at low pH employing a single-step elution using 1 M NaCl. Here, we describe an optimized purification protocol using a five-step NaCl elution to remove contaminants. The obtained nisin is devoid of impurities and shows high bactericidal activity against the nisin-sensitive L. lactis strain NZ9000. Purified nisin exhibits an IC50 of ~3 nM, which is a tenfold improvement as compared to nisin obtained via the one-step elution procedure.

  13. Nevoid basal cell carcinoma syndrome (Gorlin syndrome

    Directory of Open Access Journals (Sweden)

    Lo Muzio Lorenzo

    2008-11-01

    Full Text Available Abstract Nevoid basal cell carcinoma syndrome (NBCCS, also known as Gorlin syndrome, is a hereditary condition characterized by a wide range of developmental abnormalities and a predisposition to neoplasms. The estimated prevalence varies from 1/57,000 to 1/256,000, with a male-to-female ratio of 1:1. Main clinical manifestations include multiple basal cell carcinomas (BCCs, odontogenic keratocysts of the jaws, hyperkeratosis of palms and soles, skeletal abnormalities, intracranial ectopic calcifications, and facial dysmorphism (macrocephaly, cleft lip/palate and severe eye anomalies. Intellectual deficit is present in up to 5% of cases. BCCs (varying clinically from flesh-colored papules to ulcerating plaques and in diameter from 1 to 10 mm are most commonly located on the face, back and chest. The number of BBCs varies from a few to several thousand. Recurrent jaw cysts occur in 90% of patients. Skeletal abnormalities (affecting the shape of the ribs, vertebral column bones, and the skull are frequent. Ocular, genitourinary and cardiovascular disorders may occur. About 5–10% of NBCCS patients develop the brain malignancy medulloblastoma, which may be a potential cause of early death. NBCCS is caused by mutations in the PTCH1 gene and is transmitted as an autosomal dominant trait with complete penetrance and variable expressivity. Clinical diagnosis relies on specific criteria. Gene mutation analysis confirms the diagnosis. Genetic counseling is mandatory. Antenatal diagnosis is feasible by means of ultrasound scans and analysis of DNA extracted from fetal cells (obtained by amniocentesis or chorionic villus sampling. Main differential diagnoses include Bazex syndrome, trichoepithelioma papulosum multiplex and Torre's syndrome (Muir-Torre's syndrome. Management requires a multidisciplinary approach. Keratocysts are treated by surgical removal. Surgery for BBCs is indicated when the number of lesions is limited; other treatments include laser

  14. Feline mammary basal-like adenocarcinomas: a potential model for human triple-negative breast cancer (TNBC) with basal-like subtype

    OpenAIRE

    Wiese, David A.; Thaiwong, Tuddow; Yuzbasiyan-Gurkan, Vilma; Kiupel, Matti

    2013-01-01

    Background Breast cancer is one of the leading causes of cancer deaths. Triple-negative breast cancer (TNBC), an immunophenotype defined by the absence of immunolabeling for estrogen receptor (ER), progesterone receptor (PR) and HER2 protein, has a highly aggressive behavior. A subpopulation of TNBCs exhibit a basal-like morphology with immunohistochemical positivity for cytokeratins 5/6 (CK5/6) and/or epidermal growth factor receptor (EGFR), and have a high incidence of BRCA (breast cancer s...

  15. A basal tyrannosauroid dinosaur from the Late Jurassic of China.

    Science.gov (United States)

    Xu, Xing; Clark, James M; Forster, Catherine A; Norell, Mark A; Erickson, Gregory M; Eberth, David A; Jia, Chengkai; Zhao, Qi

    2006-02-01

    The tyrannosauroid fossil record is mainly restricted to Cretaceous sediments of Laurasia, although some very fragmentary Jurassic specimens have been referred to this group. Here we report a new basal tyrannosauroid, Guanlong wucaii gen. et sp. nov., from the lower Upper Jurassic of the Junggar Basin, northwestern China. G. wucaii is the oldest known tyrannosauroid and shows several unexpectedly primitive pelvic features. Nevertheless, the limbs of G. wucaii share several features with derived coelurosaurs, and it possesses features shared by other coelurosaurian clades. This unusual combination of character states provides an insight into the poorly known early radiation of the Coelurosauria. Notably, the presumed predatory Guanlong has a large, fragile and highly pneumatic cranial crest that is among the most elaborate known in any non-avian dinosaur and could be comparable to some classical exaggerated ornamental traits among vertebrates.

  16. Desalination of Basal Water by Mesoporous Carbons Nanocomposite Membrane.

    Science.gov (United States)

    Choi, Jeongdong; Ahn, Youngho; Gamal El-Din, Mohamed; Kim, Eun-Sik

    2016-02-01

    The hydro-transportation process used to obtain bitumen from the Alberta oil sands produces large volume of basal depressurization water (BDW), which contains high salt concentrations. In this research, thin-film nanocomposite (TFN) membrane technology applied to treat BDW in lab-scale, and evaluated water properties before and after the treatment. The average rejection ratios of ionic species were 95.2% and 92.8% by TFN membrane (with ordered mesoporous carbons (OMCs)) and thin-film composite (TFC) (without OMCs) membrane, respectively. The turbidity and total dissolved solids (TDS) were completely rejected in all treatment conditions. Interestingly, the water flux of TFN membrane was dramatically increased compared to TFC membrane. The increase of water flux was believed to be caused by the increased membrane surface hydrophilicity and nano-pore effects by the OMCs.

  17. Knockdown of GSK3β increases basal autophagy and AMPK signalling in nutrient-laden human aortic endothelial cells

    Science.gov (United States)

    Weikel, Karen A.; Cacicedo, José M.; Ruderman, Neil B.; Ido, Yasuo

    2016-01-01

    High concentrations of glucose and palmitate increase endothelial cell inflammation and apoptosis, events that often precede atherogenesis. They may do so by decreasing basal autophagy and AMP-activated protein kinase (AMPK) activity, although the mechanisms by which this occurs are not clear. Decreased function of the lysosome, an organelle required for autophagy and AMPK, have been associated with hyperactivity of glycogen synthase kinase 3β (GSK3β). To determine whether GSK3β affects nutrient-induced changes in autophagy and AMPK activity, we used a primary human aortic endothelial cell (HAEC) model of type 2 diabetes that we had previously characterized with impaired AMPK activity and autophagy [Weikel et al. (2015) Am. J. Phys. Cell Physiol. 308, C249–C263]. Presently, we found that incubation of HAECs with excess nutrients (25 mM glucose and 0.4 mM palmitate) increased GSK3β activity and impaired lysosome acidification. Suppression of GSK3β in these cells by treatment with a chemical inhibitor or overexpression of kinase-dead GSK3β attenuated these lysosomal changes. Under control and excess nutrient conditions, knockdown of GSK3β increased autophagosome formation, forkhead box protein O1 (FOXO1) activity and AMPK signalling and decreased Akt signalling. Similar changes in autophagy, AMPK and Akt signalling were observed in aortas from mice treated with the GSK3β inhibitor CHIR 99021. Thus, increasing basal autophagy and AMPK activity by inhibiting GSK3β may be an effective strategy in the setting of hyperglycaemia and dyslipidaemia for restoring endothelial cell health and reducing atherogenesis. PMID:27534430

  18. Magneto-Optical Activity in High Index Dielectric Nanoantennas

    CERN Document Server

    de Sousa, N; Sáenz, J J; García-Martín, A

    2016-01-01

    The magneto-optical activity, namely the polarization conversion capabilities of high-index, non-absorbing, core-shell dielectric nanospheres is theoretically analyzed. We show that, in analogy with their plasmonic counterparts, the polarization conversion in resonant dielectric particles is linked to the amount of electromagnetic field probing the magneto-optical material in the system. However, in strong contrast with plasmon nanoparticles, due to the peculiar distribution of the internal fields in resonant dielectric spheres, the magneto-optical response is fully governed by the magnetic (dipolar and quadrupolar) resonances with little effect of the electric ones.

  19. Highly Active Carbene Ruthenium Catalyst for Metathesis of 1-Hexene

    Institute of Scientific and Technical Information of China (English)

    BAI Chen-Xi; ZHANG Zhi-Qiang; L(U) Xiao-Bing; HE Ren; ZHANG Wen-Zhen; LU Shu-Lai

    2006-01-01

    A new carbene ruthenium complex, 1,3-bis(2,6-dimethylphenyl)-4,5-dihydroimidazol-2-ylidene)(PPh3)Cl2-Ru=CHPh, was synthesized and used as catalyst for the metathesis of 1-hexene. The resulting complex exhibited very high catalytic activity whose TOF is up to 6680 h-1. However, at the same time significant olefin isomerization was observed and could be surpressed by changing reaction conditions, such as temperature, time, alkene/Ru molar ratio and solvent.

  20. Production of N-13 labeled compounds with high specific activity

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Kazutoshi; Sasaki, Motoji; Yoshida, Yuichiro; Haradahira, Terushi; Inoue, Osamu [National Inst. of Radiological Sciences, Chiba (Japan)

    1997-03-01

    Nitrogen-13 was produced by irradiating ultra pure water saturated with a pure gas (N2, O2, He, H2) with 18 MeV protons. Ion species generated by irradiation were analyzed with radio ion chromatography systems. An automated equipment was developed to synthesize anhydrous (13N)NH3 as a synthetic precursor and (13N)p-nitrophenyl carbamate ((13N)NPC) as a model compound, using the (13N)NH3. The radiochemical yield and specific activity of (13N)NPC was high enough to carry out the receptor study with PET. (author)

  1. High dielectric constant, low loss and high photocatalytic activity in Gd doped ZnO systems

    Science.gov (United States)

    Divya, N. K.; Pradyumnan, P. P.

    2017-01-01

    Enhanced photocatalytic activity and high dielectric constant values are achieved by gadolinium (Gd) doping in ZnO. The changes that happened to the wurtzite structure of ZnO on doping are depicted in detail by using x-ray diffraction spectroscopy. The chemical composition is confirmed using energy dispersive x-ray spectroscopy (EDAX). The influence of Gd incorporation in the emission spectra of ZnO is analysed from photoluminescence studies. The photocatalytic activity enhancement occurred in ZnO system on Gd doping was explored by kinetic rate analysis. The optimum incorporation of Gd has enhanced the dielectric constant value and decreased the loss of pristine. The high dielectric constant value and low loss make the system suitable for large scale of applications in microelectronics. The work also proposes large scale synthesis of highly efficient fluorescent Gd doped ZnO photocatalysts.

  2. Basal keratin expression in breast cancer by quantification of mRNA and by immunohistochemistry

    Directory of Open Access Journals (Sweden)

    Pluciennik Elzbieta

    2010-04-01

    Full Text Available Abstract Definitions of basal-like breast cancer phenotype vary, and microarray-based expression profiling analysis remains the gold standard for the identification of these tumors. Immunohistochemical identification of basal-like carcinomas is hindered with a fact, that on microarray level not all of them express basal-type cytokeratin 5/6, 14 and 17. We compared expression of cytokeratin 5, 14 and 17 in 115 patients with operable breast cancer estimated by real-time RT-PCR and immunohistochemistry. Despite the method of dichotomization and statistical analysis, there were cases with discordant results comparing immunohistochemistry and RT-PCR analysis. For dichotomisation based on quartiles and ROC, 14% of cases were negative on immunohistochemical examination for CK5/6, but presented high CK5 mRNA levels. There were also 48-55% cases, which were CK5/6-immunopositive, but were negative by mRNA examination. Similar discordances were observed for CK14 and CK17. Basal keratin mRNAs did not correlate with ER mRNA levels, while immunohistochemistry produced significant relationship with ER status. Our observation suggest that both method may produce different results in a small proportion of cases. Discordance between immunohistochemistry and RT-PCR may confound attempts to establish a simple methods for identification of basal-like tumors.

  3. 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.

  4. Sub-Kilometer Scale Basal Roughness of the Siple Coast Ice Streams, West Antarctic Ice Sheet

    Science.gov (United States)

    Young, D. A.; Blankenship, D. D.; Peters, M. E.

    2006-12-01

    The anastomosing series of dynamic, basally lubricated ice streams found on the Siple Coast of West Antarctica play an important role in regulating the mass balance of the West Antarctic Ice Sheet (WAIS). Geological controls on lubrication, elucidated by gravity, magnetics and seismic data, have proven important in understanding the evolution of these features. An additional indicator of basal properties, the basal roughness of ice sheets, may be an indicator of crustal geology and glacial modification, as well as a controlling parameter on ice dynamics and subglacial hydrology. For the Siple Coast ice streams, Fourier analysis of > 5 kilometer morphology (Siegert et al. 2004) revealed a correlation between ice streams and low bed roughness. Coherent high resolution data allows analysis of along track roughness at tens of meters resolution (Peters et al. 2005), however these data are limited in coverage. We extend roughness estimates into to the hundreds-of-meters length scale, using both frequency domain and autocorrelation methods, using incoherent 60 MHz radio echo sounding data collected between 1991 and 1996 on a five kilometer grid. The data cover the Bentley Subglacial Trench, Bindschadler Ice Stream, Siple Dome and the onset region of Kamb Ice Stream. SAR-processed coherent sounding data collected in 2001 are used to confirm these methods. We test for confinement of ice stream rapid basal motion to distinct morphological provinces; assess the hypothesis that marine sediments blanket much of interior of the basal WAIS; and look for correlation between ice flow and textural anisotropy.

  5. 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.

  6. Minimal Role of Basal Shear Tractions in Driving Nubia-Somalia Divergence Across the East African Rift System

    Science.gov (United States)

    Stamps, D. S.; Calais, E.; Iaffaldano, G.; Flesch, L. M.

    2012-12-01

    The Nubian and Somalian plates actively diverge along the topographically high, ~5000 km long East African Rift System (EARS). As no major subduction zones bound Africa, one can assume that the forces driving the Nubia-Somalia plate system result primarily from mantle buoyancies and lateral variation in lithospheric gravitational potential energy. Images from seismic tomography and convection models suggest active mantle flow beneath Africa. However, the contribution from large-scale convection to the force balance driving plate divergence across the EARS remains in question. In this work we investigate the impact of mantle shear tractions on the dynamics of Nubia-Somalia divergence across the EARS. We compare surface motions inferred from GPS observations with strain rates and velocities predicted from dynamic models where basal shear stresses are (1) derived from forward mantle circulation models and (2) inferred from stress field boundary conditions that balance buoyancy forces in the African lithosphere. Upper mantle anisotropy derived from seismic observations beneath Africa provide independent constraints for the latter. Preliminary results suggest that basal shear tractions play a minor role in the dynamics of Nubia-Somalia divergence along the EARS. This result implies mantle-lithosphere decoupling, possibly promoted by a low viscosity asthenosphere. We corroborate the robustness of our results with estimates of upper mantle viscosity based on local upper mantle temperature estimates and rheological parameters obtained from laboratory experiments.

  7. Highly active ozonides selected against drug resistant malaria

    Science.gov (United States)

    Lobo, Lis; de Sousa, Bruno; Cabral, Lília; Cristiano, Maria LS; Nogueira, Fátima

    2016-01-01

    Ever increasing multi-drug resistance by Plasmodium falciparum is creating new challenges in malaria chemotherapy. In the absence of licensed vaccines, treatment and prevention of malaria is heavily dependent on drugs. Potency, range of activity, safety, low cost and ease of administration are crucial issues in the design and formulation of antimalarials. We have tested three synthetic ozonides NAC89, LC50 and LCD67 in vitro and in vivo against multidrug resistant Plasmodium. In vitro, LC50 was at least 10 times more efficient inhibiting P. falciparum multidrug resistant Dd2 strain than chloroquine and mefloquine and as efficient as artemisinin (ART), artesunate and dihydroartemisinin. All three ozonides showed high efficacy in clearing parasitaemia in mice, caused by multi-drug resistant Plasmodium chabaudi strains, by subcutaneous administration, demonstrating high efficacy in vivo against ART and artesunate resistant parasites. PMID:27276364

  8. Highly active ozonides selected against drug resistant malaria

    Directory of Open Access Journals (Sweden)

    Lis Lobo

    2016-01-01

    Full Text Available Ever increasing multi-drug resistance by Plasmodium falciparum is creating new challenges in malaria chemotherapy. In the absence of licensed vaccines, treatment and prevention of malaria is heavily dependent on drugs. Potency, range of activity, safety, low cost and ease of administration are crucial issues in the design and formulation of antimalarials. We have tested three synthetic ozonides NAC89, LC50 and LCD67 in vitro and in vivo against multidrug resistant Plasmodium. In vitro, LC50 was at least 10 times more efficient inhibiting P. falciparum multidrug resistant Dd2 strain than chloroquine and mefloquine and as efficient as artemisinin (ART, artesunate and dihydroartemisinin. All three ozonides showed high efficacy in clearing parasitaemia in mice, caused by multi-drug resistant Plasmodium chabaudi strains, by subcutaneous administration, demonstrating high efficacy in vivo against ART and artesunate resistant parasites.

  9. Distrofia de la membrana basal epitelial

    Directory of Open Access Journals (Sweden)

    Zaadia Pérez Parra

    Full Text Available La distrofia de Cogan es la distrofia corneal anterior más común, frecuente en adultos del sexo femenino, entre 40-70 años de edad. Presentamos un caso de una paciente de 50 años de edad, del sexo femenino, quien refiere visión borrosa, lagrimeo y fotofobia. Al examen de la córnea en lámpara de hendidura se observan imágenes de color grisáceo en forma de huellas dactilares y de mapa. Esta afección es causada por alteraciones de la membrana basal epitelial que provoca la separación parcial o total del epitelio corneal. Generalmente asintomática, es la causa más frecuente de erosión corneal recurrente. Las opciones terapéuticas varían desde lubricantes, soluciones hipertónicas tópicas, lentes de contacto de vendaje, desbridamiento del epitelio central, micropunciones mecánicas o diatermia y fotoqueratectomía con láser excímer.

  10. [Vismodegib Therapy for Periocular Basal Cell Carcinoma].

    Science.gov (United States)

    Keserü, M; Green, S; Dulz, S

    2017-01-01

    Background Basal cell carcinoma (BCC) is the commonest periorbital tumour. Mohs' micrographic surgery and secondary reconstruction is the therapeutic gold standard for periorbital BCC. In cases of inoperability for any reason, therapeutic alternatives are needed. Since the approval of vismodegib, an orally administered, targeted BCC therapy is available. Nevertheless there is little information on the use of vismodegib for periorbital BCC. Patients and Methods In a retrospective study, we analysed the data of 4 patients treated with vismodegib since 2014. The patients' mean age before starting therapy was 87 years. The mean maximum tumour diameter was 22.0 mm. Results The median follow-up was 17 months. The median treatment duration was 7.5 months. In 75 % of patients, complete clinical remission of BCC was achieved. In 25 % of patients, interim stabilisation of tumour growth was possible. The most common side effect of therapy was muscle spasm. Conclusion Vismodegib is an effective treatment option for patients with periorbital BCC, in whom surgical treatment is not possible for any reason.

  11. Distinct neurogenomic states in basal ganglia subregions relate differently to singing behavior in songbirds.

    Directory of Open Access Journals (Sweden)

    Austin T Hilliard

    Full Text Available Both avian and mammalian basal ganglia are involved in voluntary motor control. In birds, such movements include hopping, perching and flying. Two organizational features that distinguish the songbird basal ganglia are that striatal and pallidal neurons are intermingled, and that neurons dedicated to vocal-motor function are clustered together in a dense cell group known as area X that sits within the surrounding striato-pallidum. This specification allowed us to perform molecular profiling of two striato-pallidal subregions, comparing transcriptional patterns in tissue dedicated to vocal-motor function (area X to those in tissue that contains similar cell types but supports non-vocal behaviors: the striato-pallidum ventral to area X (VSP, our focus here. Since any behavior is likely underpinned by the coordinated actions of many molecules, we constructed gene co-expression networks from microarray data to study large-scale transcriptional patterns in both subregions. Our goal was to investigate any relationship between VSP network structure and singing and identify gene co-expression groups, or modules, found in the VSP but not area X. We observed mild, but surprising, relationships between VSP modules and song spectral features, and found a group of four VSP modules that were highly specific to the region. These modules were unrelated to singing, but were composed of genes involved in many of the same biological processes as those we previously observed in area X-specific singing-related modules. The VSP-specific modules were also enriched for processes disrupted in Parkinson's and Huntington's Diseases. Our results suggest that the activation/inhibition of a single pathway is not sufficient to functionally specify area X versus the VSP and support the notion that molecular processes are not in and of themselves specialized for behavior. Instead, unique interactions between molecular pathways create functional specificity in particular brain

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

    Science.gov (United States)

    Yttri, Eric A; Dudman, Joshua T

    2016-05-02

    For goal-directed behaviour it is critical that we can both select the appropriate action and learn to modify the underlying movements (for example, 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 behaviour, such as the neocortex and thalamus, are integrated with reward signalling to reinforce successful, purposive actions. The 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 and suppress actions that do not, respectively. Activity-dependent plasticity modulated by reward is thought to be sufficient for selecting actions in the striatum. Although perturbations of basal ganglia function produce profound changes in movement, it remains unknown whether activity-dependent plasticity is sufficient to produce learned changes in movement kinematics, such as velocity. Here we use cell-type-specific stimulation in mice 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 behavioural 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.

  13. The effects of dietary saturated fat on basal hypothalamic neuroinflammation in rats.

    Science.gov (United States)

    Maric, Tia; Woodside, Barbara; Luheshi, Giamal N

    2014-02-01

    Recent evidence has demonstrated that consumption of high fat diets can trigger brain inflammation and subsequent injury in the absence of any peripheral inflammatory signaling. Here we sought to investigate whether a link exists between the concentration of highly saturated fats in the diet and the development of inflammation in the brain of rats and, whether the source of the saturated fat was an important factor in this process. Adult male rats had access to diets with a moderate level of total fat (32% of calories as fat) varying in level of saturated fat [low (20%) vs high (>60%)] and its source (butter or coconut oil). After 8 weeks of diet exposure peripheral and central tissues were collected for analysis of inflammatory signals. Neither blood nor white adipose tissue exhibited any changes in inflammatory mediators regardless of the saturated fat content or the source. In the brain however, we observed significant hypothalamic upregulation of the expression of markers of glial activation as well as of interleukin (IL)-1,6 and nuclear factor (NF)-IL-6, which were highest in the group fed the butter-based diets. The increase in these inflammatory mediators had no effect on basal body temperature or the temperature response to systemic lipopolysaccharide (LPS). The present results indicate that hypothalamic inflammation associated with consumption of diets high in fat is directly linked to the saturated fat content as well as the source of that fat. These effects are likely linked to other pathophysiological changes in the regulation of metabolism.

  14. 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

  15. Great expectations: different high-risk activities satisfy different motives.

    Science.gov (United States)

    Barlow, Matthew; Woodman, Tim; Hardy, Lew

    2013-09-01

    Research on people's motives for engaging in high-risk activities has typically been viewed through the single-focused lens of sensation seeking. We provide evidence that comprehensively challenges that view. First, we develop and confirm the structure of a 3-factor measure of motives: the Sensation Seeking, Emotion Regulation, and Agency Scale (SEAS; Study 1). We then use the SEAS to provide evidence of differential motives for 2 high-risk activities: skydiving and mountaineering. The motive for skydiving is strongly associated with sensation seeking; the motive for mountaineering is strongly associated with emotion regulation and agency but not with sensation seeking (Study 2). We also show that these conclusions cannot be drawn from existing measures of personality and sensation seeking (Study 3). Finally, individuals who are motivated by emotion regulation and agency needs also have greater expectations regarding their emotion regulation and agency. It is these greater expectations that most successfully discriminate mountaineers from skydivers and control participants (Study 4). It is concluded that researchers should no longer consider risk takers as a homogenous sensation-seeking group and that they should consider risk taking as a potential model of human endeavor. The SEAS can be used as a measure of motives for behavior whenever sensation seeking, agency, or emotion regulation is thought to be at the core of such motives, and the results are discussed in the context of encouraging personality researchers to consider the specific spontaneous behaviors that motivate different people.

  16. Activated carbon fibers with a high heteroatom content by chemical activation of PBO with phosphoric acid.

    Science.gov (United States)

    Vázquez-Santos, M B; Suárez-García, F; Martínez-Alonso, A; Tascón, J M D

    2012-04-03

    The preparation of activated carbon fibers (ACFs) by phosphoric acid activation of poly(p-phenylene benzobisoxazole) (PBO) fibers was studied, with particular attention to the effects of impregnation ratio and carbonization temperature on porous texture. Phosphoric acid has a strong effect on PBO degradation, lowering the temperature range at which the decomposition takes place and changing the number of mass loss steps. Chemical analysis results indicated that activation with phosphoric acid increases the concentration of oxygenated surface groups; the resulting materials also exhibiting high nitrogen content. ACFs are obtained with extremely high yields; they have well-developed porosity restricted to the micropore and narrow mesopore range and with a significant concentration of phosphorus incorporated homogeneously in the form of functional groups. An increase in the impregnation ratio leads to increases in both pore volume and pore size, maximum values of surface area (1250 m(2)/g) and total pore volume (0.67 cm(3)/g) being attained at the highest impregnation ratio (210 wt % H(3)PO(4)) and lowest activation temperature (650 °C) used; the corresponding yield was as large as 83 wt %. The obtained surface areas and pore volumes were higher than those achieved in previous works by physical activation with CO(2) of PBO chars.

  17. Latitude migration of solar activity at high latitudes

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Utilized here is the Carte Synoptique solar filament archive,namely the catalogue of solar filaments from March 1919 to December 1989,corresponding to solar rotation numbers 876 to 1823 to study Iatitudinal migration of solar activity at high Iatitudes.Except the well-known poleward migration of solar activity from middle Iatitudes to the poles,an equatorward migration is found from the solar poles toward middle Iatitudes(about 40°)within a normal cycle,which iS neglected before,and the time interval for the former migration(4.4 years)is about 2.2 years shorter than that for the latter(6.6 years),indicating that the change from one migration to the other takes place around the maximum time of a normal cycle.In the future,a dynamo model should represent the migration from the poles toward middle Iatitudes of the Sun,besides the migration in"butterfly diagrams"and the"rush to the poles".The traditional extended activity cycle is actually a part of the period of the successive migration from the poles toward the solar equator.

  18. Effects of visual and auditory feedback on sensorimotor circuits in the basal ganglia.

    Science.gov (United States)

    Prodoehl, Janey; Yu, Hong; Wasson, Pooja; Corcos, Daniel M; Vaillancourt, David E

    2008-06-01

    Previous work using visual feedback has identified two distinct sensorimotor circuits in the basal ganglia (BG): one that scaled with the duration of force and one that scaled with the rate of change of force. The present study compared functional MRI signal changes in the BG during a grip force task using either visual or auditory feedback to determine whether the BG nuclei process auditory and visual feedback similarly. We confirmed the same two sensorimotor circuits in the BG. Activation in the striatum and external globus pallidus (GPe) scaled linearly with the duration of force under visual and auditory feedback conditions, with similar slopes and intercepts across feedback type. The pattern of signal change for the internal globus pallidus (GPi) and subthalamic nucleus (STN) was nonlinear and parameters of the exponential function were altered by feedback type. Specifically, GPi and STN activation decreased exponentially with the rate of change of force. The rate constant and asymptote of the exponential functions for GPi and STN were greater during auditory than visual feedback. In a comparison of the BOLD signal between BG regions, GPe had the highest percentage of variance accounted for and this effect was preserved for both feedback types. These new findings suggest that neuronal activity of specific BG nuclei is affected by whether the feedback is derived from visual or auditory inputs. Also, the data are consistent with the hypothesis that the GPe has a high level of information convergence from other BG nuclei, which is preserved across different sensory feedback modalities.

  19. Longitudinal Assessment of Motor Recovery of Contralateral Hand after Basal Ganglia Infarction Using Functional Magnetic Resonance Imaging

    Directory of Open Access Journals (Sweden)

    Yue Fu

    2016-01-01

    Full Text Available We used functional fMRI to study the brain activation during active finger movements at different time points during the recovery phase following basal ganglia infarction. Four hemiplegic patients with basal ganglia infarction were serially evaluated at different time points spanning the acute and chronic phase using fMRI. To evaluate motor recovery, the patients were asked to perform functional tasks arranged in a block design manner with their hand. On follow-up (chronic phase, three patients achieved significant recovery of motor function of affected limbs. Activation of bilateral sensorimotor cortex (SMC was observed in two of these patients, while activation of cerebellum was observed in all patients. No remarkable recovery of motor function was noted in one patient with left basal ganglia infarction. In this patient, the activation domain was located in SMC of both sides in acute phase and in ipsilateral SMC in chronic phase. Contralateral SMC appears to be involved in the functional rehabilitation following basal ganglia infarction. The cerebellum may act as an intermediary during functional recovery following basal ganglia infarction. The activation domain associated with active finger movement may be bilateral in acute phase; one patient was ipsilateral in the chronic stage.

  20. High-frequency TRNS reduces BOLD activity during visuomotor learning.

    Directory of Open Access Journals (Sweden)

    Catarina Saiote

    Full Text Available Transcranial direct current stimulation (tDCS and transcranial random noise stimulation (tRNS consist in the application of electrical current of small intensity through the scalp, able to modulate perceptual and motor learning, probably by changing brain excitability. We investigated the effects of these transcranial electrical stimulation techniques in the early and later stages of visuomotor learning, as well as associated brain activity changes using functional magnetic resonance imaging (fMRI. We applied anodal and cathodal tDCS, low-frequency and high-frequency tRNS (lf-tRNS, 0.1-100 Hz; hf-tRNS 101-640 Hz, respectively and sham stimulation over the primary motor cortex (M1 during the first 10 minutes of a visuomotor learning paradigm and measured performance changes for 20 minutes after stimulation ceased. Functional imaging scans were acquired throughout the whole experiment. Cathodal tDCS and hf-tRNS showed a tendency to improve and lf-tRNS to hinder early learning during stimulation, an effect that remained for 20 minutes after cessation of stimulation in the late learning phase. Motor learning-related activity decreased in several regions as reported previously, however, there was no significant modulation of brain activity by tDCS. In opposition to this, hf-tRNS was associated with reduced motor task-related-activity bilaterally in the frontal cortex and precuneous, probably due to interaction with ongoing neuronal oscillations. This result highlights the potential of lf-tRNS and hf-tRNS to differentially modulate visuomotor learning and advances our knowledge on neuroplasticity induction approaches combined with functional imaging methods.

  1. Mineralizing angiopathy with basal ganglia stroke in an infant

    Directory of Open Access Journals (Sweden)

    Puneet Jain

    2015-01-01

    Full Text Available Basal ganglia stroke is known following trivial head trauma. Recently a distinct clinic-radiological entity termed ′mineralizing angiopathy′ was described. We report an infant who developed basal ganglia stroke following trivial fall. His clinic-radiological features are described.

  2. Basal insulin and cardiovascular and other outcomes in dysglycemia

    DEFF Research Database (Denmark)

    Gerstein, Hertzel C; Bosch, Jackie; Dagenais, Gilles R

    2012-01-01

    The provision of sufficient basal insulin to normalize fasting plasma glucose levels may reduce cardiovascular events, but such a possibility has not been formally tested.......The provision of sufficient basal insulin to normalize fasting plasma glucose levels may reduce cardiovascular events, but such a possibility has not been formally tested....

  3. A Prognostic Dilemma of Basal Cell Carcinoma with Intravascular Invasion

    Science.gov (United States)

    Niumsawatt, Vachara; Castley, Andrew

    2016-01-01

    Summary: Basal cell carcinoma is the most common malignancy; however, it very rarely metastasizes. Despite the low mortality caused by this cancer, once it spreads, it has dim prognosis. We report a case of basal cell carcinoma with rare intravascular invasion and review the literature for risk factors and management of metastasis.

  4. Evolution and diversification of the basal transcription machinery.

    Science.gov (United States)

    Duttke, Sascha H C

    2015-03-01

    Transcription initiation was once thought to be regulated primarily by sequence-specific transcription factors with the basal transcription machinery being largely invariant. Gradually it became apparent that the basal transcription machinery greatly diversified during evolution and new studies now demonstrate that diversification of the TATA-binding protein (TBP) family yielded specialized and largely independent transcription systems.

  5. A functional and structural investigation of the human fronto-basal volitional saccade network

    NARCIS (Netherlands)

    Neggers, S.F.W.; Diepen, R.M. van; Zandbelt, B.B.; Vink, M.; Mandl, R.C.W.; Gutteling, T.P.

    2012-01-01

    Almost all cortical areas are connected to the subcortical basal ganglia (BG) through parallel recurrent inhibitory and excitatory loops, exerting volitional control over automatic behavior. As this model is largely based on non-human primate research, we used high resolution functional MRI and diff

  6. 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…

  7. Cutaneous head and neck basal and squamous cell carcinomas with perineural invasion

    NARCIS (Netherlands)

    Mendenhall, W.M.; Ferlito, A.; Takes, R.P.; Bradford, C.R.; Corry, J.; Fagan, J.J.; Rinaldo, A.; Strojan, P.; Rodrigo, J.P.

    2012-01-01

    Perineural invasion (PNI) occurs in 2% to 6% of cutaneous head and neck basal and squamous cell carcinomas (SCCs) and is associated with mid-face location, recurrent tumors, high histologic grade, and increasing tumor size. Patients may be asymptomatic with PNI appreciated on pathologic examination

  8. Cutaneous head and neck basal and squamous cell carcinomas with perineural invasion

    NARCIS (Netherlands)

    Mendenhall, W.M.; Ferlito, A.; Takes, R.P.; Bradford, C.R.; Corry, J.; Fagan, J.J.; Rinaldo, A.; Strojan, P.; Rodrigo, J.P.

    2012-01-01

    Perineural invasion (PNI) occurs in 2% to 6% of cutaneous head and neck basal and squamous cell carcinomas (SCCs) and is associated with mid-face location, recurrent tumors, high histologic grade, and increasing tumor size. Patients may be asymptomatic with PNI appreciated on pathologic examination

  9. COMPARATIVE ANATOMICAL STUDIES ABOUT CHICKEN SUB-BASAL CONNECTIONS

    Directory of Open Access Journals (Sweden)

    CARMEN BERGHES

    2013-07-01

    Full Text Available The studies aimed to describe the nervous formations from the base of the cranium in the hen and domestic duck. These clarifications are necessary in order to disclose some unknown facts regarding this region in the poultry species used preponderantly in laboratory studies of the aviary flu. The vegetative connections from the base of the skull have been studied on 10 poultry specimens, 5 hens and 5 ducks. The animals have been euthanatized using chloroform and a special dye has been injected through the heart in order to achieve a better differentiation of the nervous formations. Dissection was performed under a magnifying glass using instruments adequate to highly fine dissections. Photos and sketches of the dissected pieces have been taken. Nomina Anatomica (2003 was used to describe the observed formations.The studies showed that the cranial cervical ganglia around which is the sub-basal nervous tissue, is located on the border of the occipital hole, at the basis of the temporal pyramid, much deeper than in mammalians; it is better developed in the duck (3-4 mm than in the hen (1-2 mm; the cranial cervical ganglia has the shape of a globe in gallinaceans and it is long in shape in the ducks. A multitude of connecting branches were observed around the lymph node, linking it to the vague nerve, to the hypoglossal nerve, to the glossopharyngeal nerve and to the transversal paravertebral chain which is specific to poultry; an obvious branch detaches from the cranial pole, which is the sub-basal connective, while the cervical connective detaches from the caudal pole, connecting it to the cervical-thoracic lymph node.

  10. Depositional Settings of the basal López de Bertodano Formation, Maastrichtian, Antarctica Ambientes de depositación de la parte basal de la Formación López de Bertodano, Maastrichtiano, Antártida

    OpenAIRE

    E.B. Olivero; J.J. Ponce; C.A. Marsicano; D.R. Martinioni

    2007-01-01

    In Snow Hill and Seymour islands the lower Maastrichtian, basal part of the L ópez de Bertodano Formation, rests on a high relief, erosive surface elaborated in the underlying Snow Hill Island Formation. Mudstone-dominated beds with inclined heterolithic stratification dominate the basal strata of the López de Bertodano Formation. They consist of rhythmical alternations of friable sandy- and clayeymudstone couplets, with ripple cross lamination, mud drapes, and flaser bedding. They are charac...

  11. Survey of Basal Stem Rot Disease on Oil Palms (Elaeis guineensis Jacq.) in Kebun Bukit Kijang,North Sumatera, Indonesia

    Science.gov (United States)

    Lisnawita; Hanum, H.; Tantawi, A. R.

    2016-08-01

    Basal stem rot disease caused by Ganoderma sp. is a significant disease on oil palm plantations in Indonesia, especially in North Sumatera. Currently, the pathogen does not only attack the plants that have produced (old plants) but also attacks the plants that have not produced in the first generation yet. A survey of the distribution of the basal stem rot disease in the plantation of the community has been completed in order to illustrate the distribution and the incidence of the basal stem rot disease in 5 locations of the oil palm plantation of the community in Desa Bukit Kijang, Region of Asahan, North Sumatera, Indonesia. From the research, it is revealed that the basal stem rot disease has spread to all of the observed locations with the level of disease incidence between 0.71% in Kebun Bukit Kijang 3 to 50% in the 17 years old oil palm in Kebun Bukit Kijang 4 and Bukit Kijang 5. The observable symptoms of the basal stem rot disease are chlorotic leaves, the appearance of fruiting body, collapsed plants, and the existence of holes on the basal stem. The incidence of basal stem rot disease is higher on land due to a high sand content (>50%).

  12. Cyclical and patch-like GDNF distribution along the basal surface of Sertoli cells in mouse and hamster testes.

    Directory of Open Access Journals (Sweden)

    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.

  13. High sulfation and a high molecular weight are important for anti-hepcidin activity of heparin

    Directory of Open Access Journals (Sweden)

    Michela eAsperti

    2016-01-01

    Full Text Available Heparins are efficient inhibitors of hepcidin expression even in vivo, where they induce an increase of systemic iron availability. Heparins seem to act by interfering with BMP6 signaling pathways that control the expression of liver hepcidin, causing the suppression of SMAD1/5/8 phosphorylation. The anti-hepcidin activity persists also when the heparin anticoagulant property is abolished or reduced by chemical reactions of oxidation/reduction (glycol-split, Gs-Heparins or by high sulfation (SS-Heparins, but the structural characteristics needed to optimize this inhibitory activity have not been studied in detail. To this aim we analyzed three different heparins (Mucosal Heparin, the Glycol split RO-82, the partially desulfated glycol-split RO-68 and the oversulfated SSLMWH and separated them in fractions of molecular weight in the range 4-16 kD. Since the distribution of the negative charges in heparins contributes to the activity, we produced 2-O- and 6-O-desulfated heparins. These derivatives were analyzed for the capacity to inhibit hepcidin expression in hepatic HepG2 cells, in mice, and also for the capacity to bind an Heparin Binding Domain peptide. The three approaches produced consistent results and showed that the anti-hepcidin activity strongly decreases with molecular weight below 7 kD, with an increase of the N-acetylation level and after 2-O and 6-O desulfation. The high sulfation and high molecular weight properties for efficient anti-hepcidin activity suggest that heparin is involved in multiple binding sites.

  14. Pine Island Glacier - local flow mechanisms and basal sliding

    Science.gov (United States)

    Wilkens, N. M.; Kleiner, T.; Humbert, A.

    2013-12-01

    Pine Island Glacier is a fast moving outlet glacier in the West Antarctic Ice Sheet. Several tributaries feeding the central ice stream characterise the flow field structure of this glacier. In the past decades the glacier has shown acceleration, thinning and a significant grounding line retreat. These ongoing processes are coinciding with a concentrated mass loss in the area around Pine Island Glacier, the Amundsen Sea Embayment. The area is of additional interest due to its retrograde bed slope. The postulated instability of the setting turns the glacier into an even more suitable object for modelling studies. One major challenge encountered when modelling the flow field of Pine Island Glacier is to reproduce the locally varying flow pattern, with its many tributaries. Commonly this difficulty is overcome by inversion for parameters controlling basal sliding. Our study is aimed at connecting basal sliding again to physical parameters. To achieve this we conduct experiments of Pine Island Glacier with the diagnostic 3D full-Stokes model COMice. The model is thermo-mechanically coupled and implemented with the commercial finite-element package COMSOL Multiphysics©. We use remotely sensed surface velocity data to validate our results. In a first step, the model is used to identify dominant local mechanisms that drive the flow of the different tributaries. We identify connections between the basal topography, the basal temperature, the driving stress and the basal roughness distribution. The thus gained information is used to confine basal sliding. Areas with similar qualitative characteristics are identified, and constant-sliding assumptions made for those. Additionally, the basal roughness distribution is matched onto a basal sliding parameter. This way the sliding law is again brought closer to its original meaning. Our results are important for prognostic model experiments, as we connect basal sliding to locally varying basal properties, which might lead to

  15. Cholinergic Neurons Excite Cortically Projecting Basal Forebrain GABAergic Neurons

    Science.gov (United States)

    Yang, Chun; McKenna, James T.; Zant, Janneke C.; Winston, Stuart; Basheer, Radhika

    2014-01-01

    The basal forebrain (BF) plays an important role in the control of cortical activation and attention. Understanding the modulation of BF neuronal activity is a prerequisite to treat disorders of cortical activation involving BF dysfunction, such as Alzheimer's disease. Here we reveal the interaction between cholinergic neurons and cortically projecting BF GABAergic neurons using immunohistochemistry and whole-cell recordings in vitro. In GAD67-GFP knock-in mice, BF cholinergic (choline acetyltransferase-positive) neurons were intermingled with GABAergic (GFP+) neurons. Immunohistochemistry for the vesicular acetylcholine transporter showed that cholinergic fibers apposed putative cortically projecting GABAergic neurons containing parvalbumin (PV). In coronal BF slices from GAD67-GFP knock-in or PV-tdTomato mice, pharmacological activation of cholinergic receptors with bath application of carbachol increased the firing rate of large (>20 μm diameter) BF GFP+ and PV (tdTomato+) neurons, which exhibited the intrinsic membrane properties of cortically projecting neurons. The excitatory effect of carbachol was blocked by antagonists of M1 and M3 muscarinic receptors in two subpopulations of BF GABAergic neurons [large hyperpolarization-activated cation current (Ih) and small Ih, respectively]. Ion substitution experiments and reversal potential measurements suggested that the carbachol-induced inward current was mediated mainly by sodium-permeable cation channels. Carbachol also increased the frequency of spontaneous excitatory and inhibitory synaptic currents. Furthermore, optogenetic stimulation of cholinergic neurons/fibers caused a mecamylamine- and atropine-sensitive inward current in putative GABAergic neurons. Thus, cortically projecting, BF GABAergic/PV neurons are excited by neighboring BF and/or brainstem cholinergic neurons. Loss of cholinergic neurons in Alzheimer's disease may impair cortical activation, in part, through disfacilitation of BF cortically

  16. Enzymatic activity of Lecithin:retinol acyltransferase: a thermostable and highly active enzyme with a likely mode of interfacial activation.

    Science.gov (United States)

    Horchani, Habib; Bussières, Sylvain; Cantin, Line; Lhor, Mustapha; Laliberté-Gemme, Jean-Sébastien; Breton, Rock; Salesse, Christian

    2014-06-01

    Lecithin:retinol acyltransferase (LRAT) plays a major role in the vertebrate visual cycle. Indeed, it is responsible for the esterification of all-trans retinol into all-trans retinyl esters, which can then be stored in microsomes or further metabolized to produce the chromophore of rhodopsin. In the present study, a detailed characterization of the enzymatic properties of truncated LRAT (tLRAT) has been achieved using in vitro assay conditions. A much larger tLRAT activity has been obtained compared to previous reports and to an enzyme with a similar activity. In addition, tLRAT is able to hydrolyze phospholipids bearing different chain lengths with a preference for micellar aggregated substrates. It therefore presents an interfacial activation property, which is typical of classical phospholipases. Furthermore, given that stability is a very important quality of an enzyme, the influence of different parameters on the activity and stability of tLRAT has thus been studied in detail. For example, storage buffer has a strong effect on tLRAT activity and high enzyme stability has been observed at room temperature. The thermostability of tLRAT has also been investigated using circular dichroism and infrared spectroscopy. A decrease in the activity of tLRAT was observed beyond 70°C, accompanied by a modification of its secondary structure, i.e. a decrease of its α-helical content and the appearance of unordered structures and aggregated β-sheets. Nevertheless, residual activity could still be observed after heating tLRAT up to 100°C. The results of this study highly improved our understanding of this enzyme. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Novel antimicrobial peptides with high anticancer activity and selectivity.

    Directory of Open Access Journals (Sweden)

    Hung-Lun Chu

    Full Text Available We describe a strategy to boost anticancer activity and reduce normal cell toxicity of short antimicrobial peptides by adding positive charge amino acids and non-nature bulky amino acid β-naphthylalanine residues to their termini. Among the designed peptides, K4R2-Nal2-S1 displayed better salt resistance and less toxicity to hRBCs and human fibroblast than Nal2-S1 and K6-Nal2-S1. Fluorescence microscopic studies indicated that the FITC-labeled K4R2-Nal2-S1 preferentially binds cancer cells and causes apoptotic cell death. Moreover, a significant inhibition in human lung tumor growth was observed in the xenograft mice treated with K4R2-Nal2-S1. Our strategy provides new opportunities in the development of highly effective and selective antimicrobial and anticancer peptide-based therapeutics.

  18. VTEC behavior in the American sector during high solar activity

    CERN Document Server

    Ezquer, R G; Brunini, C; Conicet; Meza, A; Mosert, M; Radicella, S M

    2002-01-01

    The behavior of the vertical total electron content (VTEC) obtained from GPS signals received during the high solar activity year 1999 at stations placed in the American sector, is reported. The considered latitude range extends from 18.4 to -64.7 and the longitude ranges from 281.3 to 297.7. Median, lower and upper quartiles are used to specify variability, because they have the advantage of being less affected by large deviations that can occur during magnetic storms. The results show that the VTEC values corresponding to equinox are greater than those of solstice and that, the highest VTEC values are observed at low latitude stations. In general, the variability during daylight hours is about 30% of median or less, and that observed for nighttime hours is greater than the mentioned percentage, particularly at last hours of the night near the northern peak of the equatorial anomaly.

  19. Using Highly Interactive Virtual Environments for Safeguards Activities

    Energy Technology Data Exchange (ETDEWEB)

    Weil, Bradley S [ORNL; Alcala, Benjamin S [ORNL; Alcala, Scott [ORNL; Eipeldauer, Mary D [ORNL; Weil, Logan B [ORNL

    2010-01-01

    Highly interactive virtual environment (HIVE) is a term that refers to interactive educational simulations, serious games and virtual worlds. Studies indicate that learning with the aid of interactive environments produces better retention and depth of knowledge by promoting improved trainee engagement and understanding. Virtual reality or three dimensional (3D) visualization is often used to promote the understanding of something when personal observation, photographs, drawings, and/or sketches are not possible or available. Subjects and situations, either real or hypothetical, can be developed using a 3D model. Models can be tailored to the audience allowing safeguards and security features to be demonstrated for educational purposes in addition to engineering evaluation and performance analysis. Oak Ridge National Laboratory (ORNL) has begun evaluating the feasibility of HIVEs for improving safeguards activities such as training, mission planning, and evaluating worker task performance. This paper will discuss the development workflow of HIVEs and present some recent examples.

  20. High-resolution infrared observations of active galactic nuclei

    Science.gov (United States)

    Pott, Jörg-Uwe

    2012-07-01

    Interferometric resolution at IR wavelengths offers for the first time the possibility to zoom into the nuclei of galaxies beyond the circumnuclear stellar structures and spatially resolve gas and dust in the innermost regions (0.05-5pc), dominated by the central black hole. Ultimate goal is to reveal new aspects of AGN feeding, and interaction with its host galaxy. After first successes of resolving AGN with infrared interferometry (VLTI, Keck-IF), the second generation of high-resolution interferometric imagers behind 8m class telescopes is currently being built. I will summarize current aspects and successes of the field, and present our activities to provide extended capabilities for VLTI-Midi and -Matisse, LBT-Linc-Nirvana and Keck-Astra to study a larger sample of AGN in greater detail.

  1. High resolution dynamical mapping of social interactions with active RFID

    CERN Document Server

    Barrat, Alain; Colizza, Vittoria; Pinton, Jean-Francois; Broeck, Wouter Van den; Vespignani, Alessandro

    2008-01-01

    In this paper we present an experimental framework to gather data on face-to-face social interactions between individuals, with a high spatial and temporal resolution. We use active Radio Frequency Identification (RFID) devices that assess contacts with one another by exchanging low-power radio packets. When individuals wear the beacons as a badge, a persistent radio contact between the RFID devices can be used as a proxy for a social interaction between individuals. We present the results of a pilot study %recently performed during a conference, and a subsequent preliminary data analysis, that provides an assessment of our method and highlights its versatility and applicability in many areas concerned with human dynamics.

  2. A Case of Hyperammonemia Associated with High Dihydropyrimidine Dehydrogenase Activity

    Directory of Open Access Journals (Sweden)

    Keiki Nagaharu

    2016-01-01

    Full Text Available Over the past decades, 5-Fluorouracil (5-FU has been widely used to treat several types of carcinoma, including esophageal squamous cell carcinoma. In addition to its common side effects, including diarrhea, mucositis, neutropenia, and anemia, 5-FU treatment has also been reported to cause hyperammonemia. However, the exact mechanism responsible for 5-FU-induced hyperammonemia remains unknown. We encountered an esophageal carcinoma patient who developed hyperammonemia when receiving 5-FU-containing chemotherapy but did not exhibit any of the other common adverse effects of 5-FU treatment. At the onset of hyperammonemia, laboratory tests revealed high dihydropyrimidine dehydrogenase (DPD activity and rapid 5-FU clearance. Our findings suggested that 5-FU hypermetabolism may be one of the key mechanisms responsible for hyperammonemia during 5-FU treatment.

  3. Solvothermal syntheses of semiconductor photocatalysts of ultra-high activities

    Energy Technology Data Exchange (ETDEWEB)

    Kominami, Hiroshi; Kato, Jun-ichi; Murakami, Shin-ya; Ishii, Yoshinori; Kohno, Masaaki; Yabutani, Kei-ichi; Yamamoto, Takuhei; Kera, Yoshiya [Department of Applied Chemistry, Faculty of Science and Engineering, Kinki University, Kowakae, Higashiosaka, Osaka 577-8502 (Japan); Inoue, Masashi; Inui, Tomoyuki [Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University, Yoshida, Kyoto 606-8501 (Japan); Ohtani, Bunsho [Catalysis Research Center, Hokkaido University, Sapporo 060-0811 (Japan)

    2003-09-15

    Thermal treatment of titanium(IV) butoxide dissolved in 2-butanol at 573K under autogenous pressure (alcohothermal treatment) yielded microcrystalline anatase-type titanium(IV) oxide (TiO{sub 2}). Thermal treatment of oxobis(2,4-pentanedionato-O,O')titanium (TiO(acac){sub 2}) in ethylene glycol (EG) in the presence of sodium acetate and a small amount of water at 573K yielded microcrystalline brookite-type TiO{sub 2}. Tungsten(VI) oxide (WO{sub 3}) powders of monoclinic crystal structure with high crystallinity were synthesized by hydrothermal treatment (HTT), at 523 or 573K, of aqueous tungstic acid (H{sub 2}WO{sub 4}) solutions prepared from sodium tungstate by ion-exchange (IE) with a proton-type resin. Anatase and brookite TiO{sub 2} products were calcined at various temperatures and then used for photocatalytic mineralization of acetic acid in aqueous solutions under aerated conditions and dehydrogenation of 2-propanol under deaerated conditions. Almost all the anatase-type TiO{sub 2} samples showed the activities more than twice higher than those of representative active photocatalysts, Degussa P-25 and Ishihara ST-01 in both reactions. A brookite sample with improved crystallinity and sufficient surface area obtained by calcination at 973K exhibited the hydrogen evolution rate almost equal to P-25. HTT WO{sub 3} powders with various physical properties were used as photocatalyst for evolution of oxygen (O{sub 2}) from an aqueous silver sulfate solution. WO{sub 3} powder of high crystallinity, e.g., IE-HTT-WO{sub 3} synthesized at 573K, gave much higher O{sub 2} yield than commercially available WO{sub 3} samples.

  4. Sensor fusion methods for high performance active vibration isolation systems

    Science.gov (United States)

    Collette, C.; Matichard, F.

    2015-04-01

    Sensor noise often limits the performance of active vibration isolation systems. Inertial sensors used in such systems can be selected through a wide variety of instrument noise and size characteristics. However, the most sensitive instruments are often the biggest and the heaviest. Consequently, high-performance active isolators sometimes embed many tens of kilograms in instrumentation. The weight and size of instrumentation can add unwanted constraint on the design. It tends to lower the structures natural frequencies and reduces the collocation between sensors and actuators. Both effects tend to reduce feedback control performance and stability. This paper discusses sensor fusion techniques that can be used in order to increase the control bandwidth (and/or the stability). For this, the low noise inertial instrument signal dominates the fusion at low frequency to provide vibration isolation. Other types of sensors (relative motion, smaller but noisier inertial, or force sensors) are used at higher frequencies to increase stability. Several sensor fusion configurations are studied. The paper shows the improvement that can be expected for several case studies including a rigid equipment, a flexible equipment, and a flexible equipment mounted on a flexible support structure.

  5. Highly active and efficient catalysts for alkoxycarbonylation of alkenes

    Science.gov (United States)

    Dong, Kaiwu; Fang, Xianjie; Gülak, Samet; Franke, Robert; Spannenberg, Anke; Neumann, Helfried; Jackstell, Ralf; Beller, Matthias

    2017-01-01

    Carbonylation reactions of alkenes constitute the most important industrial processes in homogeneous catalysis. Despite the tremendous progress in this transformation, the development of advanced catalyst systems to improve their activity and widen the range of feedstocks continues to be essential for new practical applications. Herein a palladium catalyst based on 1,2-bis((tert-butyl(pyridin-2-yl)phosphanyl)methyl)benzene L3 (pytbpx) is rationally designed and synthesized. Application of this system allows a general alkoxycarbonylation of sterically hindered and demanding olefins including all kinds of tetra-, tri- and 1,1-disubstituted alkenes as well as natural products and pharmaceuticals to the desired esters in excellent yield. Industrially relevant bulk ethylene is functionalized with high activity (TON: >1,425,000 TOF: 44,000 h-1 for initial 18 h) and selectivity (>99%). Given its generality and efficiency, we expect this catalytic system to immediately impact both the chemical industry and research laboratories by providing a practical synthetic tool for the transformation of nearly any alkene into a versatile ester product.

  6. Exotic high activity surface patterns in PtAu nanoclusters

    KAUST Repository

    Mokkath, Junais Habeeb

    2013-05-09

    The structure and chemical ordering of PtAu nanoclusters of 79, 135, and 201 atoms are studied via a combination of a basin hopping atom-exchange technique (to locate the lowest energy homotops at fixed composition), a symmetry orbit technique (to find the high symmetry isomers), and density functional theory local reoptimization (for determining the most stable homotop). The interatomic interactions between Pt and Au are derived from the empirical Gupta potential. The lowest energy structures show a marked tendency toward PtcoreAushell chemical ordering by enrichment of the more cohesive Pt in the core region and of Au in the shell region. We observe a preferential segregation of Pt atoms to (111) facets and Au atoms to (100) facets of the truncated octahedron cluster motif. Exotic surface patterns are obtained particularly for Pt-rich compositions, where Pt atoms are being surrounded by Au atoms. These surface arrangements boost the catalytic activity by creating a large number of active sites. © 2013 American Chemical Society.

  7. Mathematical modelling of p53 basal dynamics and DNA damage response.

    Science.gov (United States)

    Chong, Ket Hing; Samarasinghe, Sandhya; Kulasiri, Don

    2015-01-01

    The p53 tumour suppressor protein is a transcription factor that activates genes that result in cell cycle arrest, DNA damage repair, senescence or apoptosis. Recent individual cell studies have indicated that p53 activation is highly regulated in response to stressed conditions and non-stressed (normal proliferating) conditions in cells. The aim of this research is to investigate the design principles behind the precise regulation of p53 activation, under normal and stressed conditions. We extended the Sun et al. (2011) mathematical model of delay differential equations by incorporating the most recently found molecular interactions and hypotheses. In particular, we found that the core regulatory network consists of ATM, Mdm2, MdmX, Wip1 and p53. Our model of the p53 core regulatory feedback mechanisms can reproduce a series of repeated pulses in stressed conditions with appropriate induction of cell cycle arrest, and one or two spontaneous pulses (basal dynamics) in non-stressed conditions and these are consistent with the recent experimental findings. Our results show that the p53 spontaneous pulses are due to intrinsic DNA double strand breaks in normal proliferating cells, and p53 auto-regulation (positive feedback loop) allows threshold activation of p53 in generating these pulses. It also shows that the p53 dynamics are excitable; bifurcation analysis revealed a spectrum of p53 behaviour under stressed and non-stressed (normal) conditions on the basis of stress signal activation rate, and characterised p53 dynamics as Type II excitability. Additionally, the model makes testable predictions on pharmacological intervention to reactivate p53. Importantly, we reveal novel findings on the mechanism of threshold activation of p53 pulsatile and oscillatory dynamics that are important for its physiological function as the guardian of the genome.

  8. On the Evolution of High-Redshift Active Galactic Nuclei

    CERN Document Server

    Mao, Jirong

    2016-01-01

    We build a simple physical model to study the high-redshift active galactic Nucleus (AGN) evolution within the co-evolution framework of central black holes (BHs) and their host galaxies. The correlation between the circular velocity of a dark halo $V_c$ and the velocity dispersion of a galaxy $\\sigma$ is used to link the dark matter halo mass and BH mass. The dark matter halo mass function is converted to the BH mass function for any given redshift. The high-redshift optical AGN luminosity functions (LFs) are constructed. At $z\\sim 4$, the flattening feature is not shown at the faint end of the optical AGN LF. This is consistent with observational results. If the optical AGN LF at $z\\sim 6$ can be reproduced in the case in which central BHs have the Eddington-limited accretion, it is possible for the AGN lifetime to have a small value of $2\\times 10^5$ yrs. The X-ray AGN LFs and X-ray AGN number counts are also calculated at $2.03$, respectively, using the same parameters adopted in the calculation for the o...

  9. Predição da frequência cardíaca basal de indivíduos com níveis de atividade física alto e baixo Prediction of baseline heart rate of individuals with different levels of habitual physical activity

    Directory of Open Access Journals (Sweden)

    André de Assis Lauria

    2013-02-01

    its measurement, the objective was to propose an equation for predicting HR Basal. Therefore, at first, it was necessary to describe the pattern of rhythmicity of HR and study the influence of habitual physical activity level (PAL on this rhythmicity. METHOD: 90 subjects (54 men and 36 women filled out the Baecke Questionnaire, median was used to form the PAL A and PAL B groups. The subjects self-assessed HRres at 6, 9, 12, 15, 18, 21 and 24 h using a cardio frequency meter. To describe the rhythmicity and identify the PAL influence, ANOVA followed by Tukey test (p> 0.05 were applied for absolute and normalized values of HRres. The normalized values were adjusted by second-order polynomial to construct the prediction equation, whose validity was tested by Pearson correlation (p> 0.05 and standard error of estimate (SEE. RESULTS: HRres in bpm, of the PAL A group was lower than in the PAL B group at all moments tested: 60 ± 7.5, 64 ± 9.3, 63 ± 8.1, 66 ± 8.7, 66 ± 7,7, 64 and 60 ± 8.1 ± 8.2 compared to: 66 ± 9.6, 11.4 ± 71, 72 ± 11.6, 73 ± 10.8, 10.7 ± 74, 69 ± 9.4 and 10.7 ± 68. Concerning normalized values, no significant differences were found between the two groups and both showed rhythmicity similar to a parabola. The prediction equation showed r 0.70 to 0.83 and SEE from 4.8 to 6.2 bpm. CONCLUSION: HRres presents lower values in more active individuals, but with the same pattern of rhythmicity. This equation enables prediction of FCbasal from the measurement of HRres taken at different times of day.

  10. Highly active antiretroviral therapy: Does it Sound toxic?

    Directory of Open Access Journals (Sweden)

    Katijah Khoza-Shangase

    2011-01-01

    Full Text Available Objective : The main objective of the current study is to monitor the auditory status in a group of adults with AIDS, receiving Highly Active Antiretroviral Therapy (HAART (3TC -lamivudine, D4T - stavudine, and efavirenz in a hospital outpatient clinic in Gauteng. A total sample of 54 adults (between the ages of 18 and 50 years in the experimental group and 16 in the control group were assessed prospectively following a repeated measures design. All participants were assessed at baseline at three months, and at six months into the treatment. Materials and Methods : The participants underwent case history interviews and medical record reviews, otoscopy, and tympanometry, as well as conventional pure tone audiometry and distortion product otoacoustic emission testing. Both descriptive and inferential statistics were used to analyze the data. Results : On audiological monitoring, statistically significant changes (P<0.05 were established, only in the experimental group, for pure tone audiometry - with clinically significant changes found at high frequencies. Statistically significant changes with clinically significant changes were obtained for distortion product otoacoustic emissions (DPOAEs in the experimental group, particularly at high frequencies - implying subclinical hearing function changes; while lack of statistically significant changes with no clinically significant changes were found in the control group. The subclinical hearing changes in the experimental group were also evident in the findings of the subclinical hearing loss group, who, although they had normal pure tone function after six months of follow up, presented with clinical changes on DPOAEs at 6 and 8 kHz. Conclusions : Findings highlight the need for closer monitoring of the effects of antiretroviral drugs (ARVs on hearing, through the use of more sensitive tools of assessment when conducting drug trials.

  11. β-Spectrin regulates the hippo signaling pathway and modulates the basal actin network.

    Science.gov (United States)

    Wong, Kenneth Kin Lam; Li, Wenyang; An, Yanru; Duan, Yangyang; Li, Zhuoheng; Kang, Yibin; Yan, Yan

    2015-03-01

    Emerging evidence suggests functional regulation of the Hippo pathway by the actin cytoskeleton, although the detailed molecular mechanism remains incomplete. In a genetic screen, we identified a requirement for β-Spectrin in the posterior follicle cells for the oocyte repolarization process during Drosophila mid-oogenesis. β-spectrin mutations lead to loss of Hippo signaling activity in the follicle cells. A similar reduction of Hippo signaling activity was observed after β-Spectrin knockdown in mammalian cells. We further demonstrated that β-spectrin mutations disrupt the basal actin network in follicle cells. The abnormal stress fiber-like actin structure on the basal side of follicle cells provides a likely link between the β-spectrin mutations and the loss of the Hippo signaling activity phenotype.

  12. Sensitizing basal-like breast cancer to chemotherapy using nanoparticles conjugated with interference peptide

    Science.gov (United States)

    Sorolla, A.; Ho, D.; Wang, E.; Evans, C. W.; Ormonde, C. F. G.; Rashwan, R.; Singh, R.; Iyer, K. Swaminathan; Blancafort, P.

    2016-04-01

    Basal-like breast cancers are highly aggressive malignancies associated with very poor prognosis. Although these cancers may initially respond to first-line treatment, they become highly resistant to standard chemotherapy in the metastatic setting. Chemotherapy resistance in basal-like breast cancers is associated with highly selective overexpression of the homeobox transcription factor Engrailed 1 (EN1). Herein, we propose a novel therapeutic strategy using poly(glycidyl methacrylate) nanoparticles decorated with poly(acrylic acid) that enable dual delivery of docetaxel and interference peptides designed to block or inhibit EN1 (EN1-iPep). We demonstrate that EN1-iPep is highly selective in inducing apoptotic cell death in basal-like cancer cells with negligible effects in a non-neoplastic human mammary epithelial cell line. Furthermore, we show that treatment with EN1-iPep results in a highly synergistic pharmacological interaction with docetaxel in inhibiting cancer cell growth. The incorporation of these two agents in a single nanoformulation results in greater anticancer efficacy than current nanoparticle-based treatments used in the clinical setting.Basal-like breast cancers are highly aggressive malignancies associated with very poor prognosis. Although these cancers may initially respond to first-line treatment, they become highly resistant to standard chemotherapy in the metastatic setting. Chemotherapy resistance in basal-like breast cancers is associated with highly selective overexpression of the homeobox transcription factor Engrailed 1 (EN1). Herein, we propose a novel therapeutic strategy using poly(glycidyl methacrylate) nanoparticles decorated with poly(acrylic acid) that enable dual delivery of docetaxel and interference peptides designed to block or inhibit EN1 (EN1-iPep). We demonstrate that EN1-iPep is highly selective in inducing apoptotic cell death in basal-like cancer cells with negligible effects in a non-neoplastic human mammary

  13. Cytosolic BNIP3 Dimer Interacts with Mitochondrial BAX Forming Heterodimers in the Mitochondrial Outer Membrane under Basal Conditions.

    Science.gov (United States)

    Hendgen-Cotta, Ulrike B; Esfeld, Sonja; Rudi, Katharina; Miinalainen, Ilkka; Klare, Johann P; Rassaf, Tienush

    2017-03-23

    The primary function of mitochondria is energy production, a task of particular importance especially for cells with a high energy demand like cardiomyocytes. The B-cell lymphoma (BCL-2) family member BCL-2 adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) is linked to mitochondrial targeting after homodimerization, where it functions in inner membrane depolarization and permeabilization of the mitochondrial outer membrane (MOM) mediating cell death. We investigated the basal distribution of cardiac BNIP3 in vivo and its physical interaction with the pro-death protein BCL2 associated X, apoptosis regulator (BAX) and with mitochondria using immunoblot analysis, co-immunoprecipitation, and continuous wave and pulsed electron paramagnetic resonance spectroscopy techniques. We found that BNIP3 is present as a dimer in the cytosol and in the outer membrane of cardiac mitochondria under basal conditions. It forms disulfide-bridged, but mainly non-covalent dimers in the cytosol. Heterodimers with BAX are formed exclusively in the MOM. Furthermore, our results suggest that BNIP3 interacts with the MOM directly via mitochondrial BAX. However, the physical interactions with BAX and the MOM did not affect the membrane potential and cell viability. These findings suggest that another stimulus other than the mere existence of the BNIP3/BAX dimer in the MOM is required to promote BNIP3 cell-death activity; this could be a potential disturbance of the BNIP3 distribution homeostasis, namely in the direction of the mitochondria.

  14. 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.

  15. Basal debris entrainment and transport in glaciers of southwestern Bylot Island, Canadian Arctic

    Science.gov (United States)

    Zdanowicz, C.M.; Michel, F.A.; Shilts, W.W.

    1996-01-01

    Glaciers on southwestern Bylot Island in the Canadian Arctic flow from an alpine setting in high-grade crystalline Archean terrane, on to coastal lowlands underlain by clastic sedimentary strata of Cretaceous to Tertiary age. We have used the contrasting mineralogy of the substrate as a tool to study subglacial entrainment and transport of debris in two large piedmont glaciers on Bylot Island. High chlorite/ and mica-illite/smectite ratios indicate that most basal debris is derived from crystalline rocks underlying the upper reaches of the glaciers. The subglacial accretion of Cretaceous-Tertiary sediments appears restricted to the lowermost part of the basal zone and is most noticeable near the glaciers' termini. Ice associated with discrete silty-sandy debris layers is characterized by an isotopic signature indicative of refreezing of meltwater at the glacier sole. The compositional, textural and isotopic characteristics of basal sediment and ice lead us to conclude that subglacial entrainment through basal ice accretion occurs in both the upper and marginal parts of the glaciers.

  16. Preparation of activated carbon with high surface area for high-capacity methane storage

    Institute of Scientific and Technical Information of China (English)

    Bingsi Liua; Wenshuo Wanga; Na Wanga; Peter Chak Tong Aub

    2014-01-01

    Activated carbon (AC) was fabricated from corncob, which is cheap and abundant. Experimental parameters such as particle size of corncob, KOH/char weight ratio, and activation temperature and time were optimized to generate AC, which shows high methane sorption capacity. AC has high specific surface area (3227 m2/g), with pore volume and pore size distribution equal to 1.829 cm3/g and ca. 1.7-2.2 nm, respectively. Under the condition of 2◦C and less than 7.8 MPa, methane sorption in the presence of water (Rw=1.4) was as high as 43.7 wt%methane per unit mass of dry AC. The result is significantly higher than those of coconut-derived AC (32 wt%) and ordered mesoporous carbon (41.2 wt%, Rw=4.07) under the same condition. The physical properties and amorphous chaotic structure of AC were characterized by N2 adsorption isotherms, XRD, SEM and HRTEM. Hence, the corncob-derived AC can be considered as a competitive methane-storage material for vehicles, which are run by natural gas.

  17. Evidence of solar induced cycles of high seismic activity

    Science.gov (United States)

    Duma, G.

    2010-12-01

    In the past century, several observational results and corresponding publications indicate a systematic seismic performance with respect to the time of day and seasons as well. Such effects could be caused only by solar or lunar influence. In addition, a possible relation with the solar cycles was discussed in some papers, too. Intensive studies on these topics have also been performed at the Central Institute for Meteorology and Geodynamics (ZAMG), Vienna, Austria. They strongly confirm the above mentioned effects. In order to verify a solar influence on earthquake activity correlations were performed between the three-hour magnetic index Kp and the energy release of earthquakes in the long term. Kp characterizes the magnetic field disturbances which are mainly caused by the solar particle radiation, the solar wind. Kp is determined on a routine basis from magnetic records of 13 observatories worldwide and is continuously published by ISGI, France. Three regions of continental size were investigated, using the USGS (PDE) earthquake catalogue data, from 1974 on: N-America, S-America and Eurasia. The statistic analyses reveal that from 1974 to 2009 the index Kp varies in cycles with periods between 9 and 12 years, somewhat different to the sunspot number cycles (no. 21, 22, 23) of 11 years. As to the seismic energy release, the sqrt (energy E) of an event is taken as measure, which relates to the ‘strain release’ due to the earthquake (Benioff). For Kp the monthly averages were computed, for the strain release the monthly sums of sqrt(E), hereinafter referred to as STR. From the statistic estimates of the relation Kp-STR for all the three regions N-America, S-America and Eurasia it becomes evident, that the correlation is highly significant: earthquake activity, quantified by the monthly STR, follows the Kp cycles with high coincidence. A quantitative analysis reveals that on an annual basis, the sum of released energy by earthquakes changes by a factor up to

  18. High Efficiency Interleaved Active Clamped Dc-Dc Converter with Fuel Cell for High Voltage Applications

    Directory of Open Access Journals (Sweden)

    Sona P

    2014-02-01

    Full Text Available A high efficiency interleaved ZVS active clamped current fed dc-dc converter is proposed in this paper specially used for fuel cell applications. As the fuel cell output is very low we are in need of a step up dc-dc converter. Here a current fed dc-dc converter is used. Two current fed dc-dc converters are interleaved by connecting their inputs in parallel and outputs in series. With this proposed methodology input current ripples in the fuel cell stacks can be reduced and a regulated output voltage ripples can be obtained. The active clamping circuit used in this model absorbs the turn off voltage spikes hence low voltage devices with low on state resistance can be used.Voltage doubler circuits will give double the output voltage than normal with smaller transformer turns ratio and flexibility. The proposed method is simulated in MATLAB for verifying the accuracy of the proposed design.

  19. On the Evolution of High-redshift Active Galactic Nuclei

    Science.gov (United States)

    Mao, Jirong; Kim, Minsun

    2016-09-01

    We build a simple physical model to study the high-redshift active galactic nucleus (AGN) evolution within the co-evolution framework of central black holes (BHs) and their host galaxies. The correlation between the circular velocity of a dark halo V c and the velocity dispersion of a galaxy σ is used to link the dark matter halo mass and BH mass. The dark matter halo mass function is converted to the BH mass function for any given redshift. The high-redshift optical AGN luminosity functions (LFs) are constructed. At z˜ 4, the flatt