758 research outputs found

    Heat tolerance in a wild Oryza species is attributed to maintenance of Rubisco activation by a thermally stable Rubisco activase ortholog

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    • The response of photosynthesis and plant growth to short periods of supra-optimal heat was tested in rice (Oryza sativa) and two wild Oryza species from the Australian savanna, O. meridionalis and O. australiensis. The mechanism of heat tolerance in the wild species was explored, particularly focusing on the heat-labile protein Rubisco activase (RCA). • We compared leaf elongation rates, net photosynthesis and Rubisco activation state at moderate (28°C) and high temperature (45°C). Sequence analysis followed by enzyme kinetics of RCA was used to identify structural differences and thermal stability. • Oryza australiensis was the most heat-tolerant species. Rubisco activation state was positively correlated with leaf elongation rates across all three species at four times following exposure to 45°C. Oryza australiensis had multiple polymorphisms in the RCA primary protein sequence, and the protein was thermally stable up to 42°C relative to RCA from O. sativa which became inhibited at 36°C. • We attribute the heat tolerance of growth and photosynthesis in these wild species to thermal stability of RCA, enabling Rubisco to remain active. Because thermal stability of RCA in O. australiensis co-occurs with reduced enzyme specific activity, an increased RCA to Rubisco ratio is required in vivo to maintain high Rubisco activation

    Response control networks are selectively modulated by attention to rare events and memory load regardless of the need for inhibition

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    Recent evidence has sparked debate about the neural bases of response selection and inhibition. In the current study, we employed two reactive inhibition tasks, the Go/Nogo (GnG) and Simon tasks, to examine questions central to these debates. First, we investigated whether a fronto-cortical-striatal system was sensitive to the need for inhibition per se or the presentation of infrequent stimuli, by manipulating the proportion of trials that do not require inhibition (Go/Compatible trials) relative to trials that require inhibition (Nogo/Incompatible trials). A cortico-subcortical network composed of insula, putamen, and thalamus showed greater activation on salient and infrequent events, regardless of the need for inhibition. Thus, consistent with recent findings, key parts of the fronto-cortical-striatal system are engaged by salient events and do not appear to play a selective role in response inhibition. Second, we examined how the fronto-cortical-striatal system is modulated by working memory demands by varying the number of stimulus-response (SR) mappings. Right inferior parietal lobule showed decreasing activation as the number of SR mappings increased, suggesting that a form of associative memory - rather than working memory - might underlie performance in these tasks. A broad motor planning and control network showed similar trends that were also modulated by the number of motor responses required in each task. Finally, bilateral lingual gyri were more robustly engaged in the Simon task, consistent with the role of this area in shifts of visuo-spatial attention. The current study sheds light on how the fronto-cortical-striatal network is selectively engaged in reactive control tasks and how control is modulated by manipulations of attention and memory load

    Inhibiting androgen receptor nuclear entry in castration-resistant prostate cancer

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    Clinical resistance to the second-generation antiandrogen enzalutamide in castration resistant prostate cancer (CRPC), despite persistent androgen receptor (AR) activity in tumors, highlights the unmet medical need for next generation antagonists. We have identified and characterized tetra-aryl cyclobutanes (CBs) as a new class of competitive AR antagonists that exhibit a unique mechanism of action. These CBs are structurally distinct from current antiandrogens (hydroxyflutamide, bicalutamide, and enzalutamide), and inhibit AR-mediated gene expression, cell proliferation, and tumor growth in several models of CRPC. Conformational profiling revealed that CBs stabilize an AR conformation resembling an unliganded receptor. Using a variety of techniques, it was determined that the AR:CB complex was not recruited to AR-regulated promoters and, like apo AR, remains sequestered in the cytoplasm bound to heat shock proteins. Thus, we have identified third generation AR antagonists whose unique mechanism of action suggests that they may have therapeutic potential in CRPC

    Appropriateness to set a group health based guidance value for T2 and HT2 toxin and its modified forms

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    Acknowledgements: The Panel wishes to thank the members of the Working Group on HBGV for mycotoxins and their modified forms: Jan Alexander, Chiara Dall'Asta, Arno Gutleb, Manfred Metzler, Isabelle Oswald and Dominique Parent-Massin for the preparatory work on this scientific opinion, and the EFSA staff members: Marco Binaglia and Hans Steinkellner for the support provided to this scientific opinion.Peer reviewedPublisher PD

    Appropriateness to set a group health based guidance value for nivalenol and its modified forms

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    The Panel wishes to thank the members of the Working Group on HBGV for mycotoxins and their modified forms: Jan Alexander, Chiara Dall'Asta, Arno Gutleb, Manfred Metzler, Isabelle P Oswald and Dominique Parent‐Massin for the preparatory work on this scientific output, and the EFSA staff members: Marco Binaglia and Hans Steinkellner for the support provided to this scientific output. Adopted: 15 March 2017Peer reviewedPublisher PD

    Subthalamic nucleus stimulation affects orbitofrontal cortex in facial emotion recognition: a pet study

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    Deep brain stimulation (DBS) of the bilateral subthalamic nucleus (STN) in Parkinson's disease is thought to produce adverse events such as emotional disorders, and in a recent study, we found fear recognition to be impaired as a result. These changes have been attributed to disturbance of the STN's limbic territory and would appear to confirm that the negative emotion recognition network passes through the STN. In addition, it is now widely acknowledged that damage to the orbitofrontal cortex (OFC), especially the right side, can result in impaired recognition of facial emotions (RFE). In this context, we hypothesized that this reduced recognition of fear is correlated with modifications in the cerebral glucose metabolism of the right OFC. The objective of the present study was first, to reinforce our previous results by demonstrating reduced fear recognition in our Parkinson's disease patient group following STN DBS and, second, to correlate these emotional performances with glucose metabolism using 18FDG-PET. The 18FDG-PET and RFE tasks were both performed by a cohort of 13 Parkinson's disease patients 3 months before and 3 months after surgery for STN DBS. As predicted, we observed a significant reduction in fear recognition following surgery and obtained a positive correlation between these neuropsychological results and changes in glucose metabolism, especially in the right OFC. These results confirm the role of the STN as a key basal ganglia structure in limbic circuits

    Effects of estrogen agonists on amphetamine-stimulated striatal dopamine release

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    Based upon the observation that estrogen acts in the striatum to rapidly modulate dopamine (DA) neural transmission and DA-mediated behaviors, it has been postulated that these effects of estrogen are mediated by a specific, membrane-bound receptor mechanism. To further characterize the pharmacological specificity of the estrogen binding site, the present experiments examine effects of various estrogen agonists on amphetamine (AMPH)-induced DA release from striatal tissue of ovariectomized female rats, using a superfusion method. Catechol estrogens 4-, and 2-hydroxyestradiol, but not 2-methoxyestradiol, significantly enhance AMPH-induced striatal DA release. Estrogen metabolites, estrone and estriol, and the non-steroidal estrogen analog, diethylstilbestrol, are without effects. Estradiol conjugated to bovine serum albumin (BSA) mimics the effect of estradiol to enhance stimulated striatal DA release. These results indicate that the steroidal configuration and hydroxylation on the A-ring of estrogenic compounds may be important determinants of ligand binding to the putative estrogen binding site in the striatum. Furthermore, the effectiveness of the estradiol conjugated to BSA reinforces the idea of an external membrane-bound receptor binding site in the striatum. Synapse 29:379–391, 1998. © 1998 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34982/1/10_ftp.pd

    Immunotoxin-Mediated Tract Targeting in the Primate Brain: Selective Elimination of the Cortico-Subthalamic “Hyperdirect” Pathway

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    Using a neuron-specific retrograde gene-transfer vector (NeuRet vector), we established immunotoxin (IT)-mediated tract targeting in the primate brain that allows ablation of a neuronal population constituting a particular pathway. Here, we attempted selective removal of the cortico-subthalamic “hyperdirect” pathway. In conjunction with the direct and indirect pathways, the hyperdirect pathway plays a crucial role in motor information processing in the basal ganglia. This pathway links the motor-related areas of the frontal lobe directly to the subthalamic nucleus (STN) without relay at the striatum. After electrical stimulation in the motor-related areas such as the supplementary motor area (SMA), triphasic responses consisting of an early excitation, an inhibition, and a late excitation are usually detected in the internal segment of the globus pallidus (GPi). Several lines of pharmacophysiological evidence suggest that the early excitation may be derived from the hyperdirect pathway. In the present study, the NeuRet vector expressing human interleukin-2 receptor α-subunit was injected into the STN of macaque monkeys. Then, IT injections were made into the SMA. In these monkeys, single-neuron activity in the GPi was recorded in response to the SMA stimulation. We found that the early excitation was largely reduced, with neither the inhibition nor the late excitation affected. The spontaneous firing rate and pattern of GPi neurons remained unchanged. This indicates that IT-mediated tract targeting successfully eliminated the hyperdirect pathway selectively from the basal ganglia circuitry without affecting spontaneous activity of STN neurons. The electrophysiological finding was confirmed with anatomical data obtained from retrograde and anterograde neural tracings. The present results define that the cortically-driven early excitation in GPi neurons is mediated by the hyperdirect pathway. The IT-mediated tract targeting technique will provide us with novel strategies for elucidating various neural network functions
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