bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overexpression ofMtCAS31enhances drought tolerance in transgenic Arabidopsis by reducing stomatal density
Authors: Xie Can , Zhang Rongxue , Qu Yueting , Miao Zhenyan , Zhang Yunqin , Shen Xiaoye , Wang Tao , Dong Jiangli 
Published: April 2012

SummaryDehydrins are a type of late embryogenesis abundant protein. Some dehydrins are involved in the response to various abiotic stresses. Accumulation of dehydrins enhances the drought, cold and salt tolerances of transgenic plants, although the underlying mechanism is unclear. MtCAS31 (Medicago Truncatulacold‐acclimation specific protein 31) is a Y2K4‐type dehydrin that was isolated fromMedicago truncatula.We analyzed the subcellular and histochemical localization ofMtCAS31, and the expression patterns ofMtCAS31under different stresses. Transgenic Arabidopsis that overexpressedMtCAS31was used to determine the function ofMtCAS31. A yeast two‐hybrid assay was used to screen potential proteins that could interact with MtCAS31. The interaction was confirmed by bimolecular fluorescence complementation (BiFC) assay.After a 3‐h drought treatment, the expression ofMtCAS31significantly increased 600‐fold.MtCAS31overexpression dramatically reduced stomatal density and markedly enhanced the drought tolerance of transgenic Arabidopsis. MtCAS31 could interact with AtICE1 (inducer of CBF expression 1) and the AtICE1 homologous protein Mt7g083900.1, which was identified fromMedicago truncatulabothin vitroandin vivo.Our findings demonstrate that a dehydrin induces decreased stomatal density. Most importantly, the interaction of MtCAS31 with AtICE1 plays a role in stomatal development. We hypothesize that the interaction of MtCAS31 and AtICE1 caused the decrease in stomatal density to enhance the drought resistance of transgenic Arabidopsis.
Iranians’ contribution to world literature on neuroscience
Authors: Ashrafi Farzad , Mohammadhassanzadeh Hafez , Shokraneh Farhad , Valinejadi Ali , Johari Karim , Saemi Nazanin , Zali Alireza , Mohaghegh Niloofar , Ashayeri Hassan 
Published: April 2012

AbstractObjective:  The purpose of this study is to analyse Iranian scientific publications in the neuroscience subfields by librarians and neuroscientists, using Science Citation Index Expanded (SCIE) via Web of Science data over the period, 2002–2008.Methods:  Data were retrieved from the SCIE. Data were collected from the ‘subject area’ of the database and classified by neuroscience experts into 14 subfields. To identify the citation patterns, we applied the ‘impact factor’ and the ‘number of publication’. Data were also analysed using HISTCITE, Excel 2007 and SPSS.Results:  Seven hundred and thirty‐four papers have been published by Iranian between 2002 and 2008. Findings showed a growing trend of neuroscience papers in the last 3 years with most papers (264) classified in the neuropharmacology subfield. There were fewer papers in neurohistory, psychopharmacology and artificial intelligence. International contributions of authors were mostly in the neurology subfield, and ‘Collaboration Coefficient’ for the neuroscience subfields in Iran was 0.686 which is acceptable. Most international collaboration between Iranians and developed countries was from USA. Eighty‐seven percent of the published papers were in journals with the impact factor between 0 and 4; 25% of papers were published by the researchers affiliated to Tehran University of Medical Sciences.Conclusion:  Progress of neuroscience in Iran is mostly seen in the neuropharmacology and the neurology subfields. Other subfields should also be considered as a research priority by health policymakers. As this study was carried out by the collaboration of librarians and neuroscientists, it has been proved valuable for both librarians and policymakers. This study may be encouraging for librarians from other developing countries.
The heat shock transcription factor Hsf1 is downregulated in DNA damage–associated senescence, contributing to the maintenance of senescence phenotype
Authors: Kim Geunwon , Meriin Anatoli B. , Gabai Vladimir L. , Christians Elisabeth , Benjamin Ivor , Wilson Andrew , Wolozin Benjamin , Sherman Michael Y. 
Published: April 2012

SummaryHeat shock response (HSR) that protects cells from proteotoxic stresses is downregulated in aging, as well as upon replicative senescence of cells in culture. Here we demonstrate that HSR is suppressed in fibroblasts from the patients with segmental progerioid Werner Syndrome, which undergo premature senescence. Similar suppression of HSR was seen in normal fibroblasts, which underwent senescence in response to DNA damaging treatments. The major DNA‐damage‐induced signaling (DDS) pathways p53–p21 and p38‐NF‐kB‐SASP contributed to the HSR suppression. The HSR suppression was associated with inhibition of both activity and transcription of the heat shock transcription factor Hsf1. This inhibition in large part resulted from the downregulation of SIRT1, which in turn was because of decrease in the expression of the translation regulator HuR. Importantly, we uncovered a positive feedback regulation, where suppression of Hsf1 further activates the p38–NF‐κB‐SASP pathway, which in turn promotes senescence. Overexpression of Hsf1 inhibited the p38–NFκB‐SASP pathway and partially relieved senescence. Therefore, downregulation of Hsf1 plays an important role in the development or in the maintenance of DNA damage signaling‐induced cell senescence.
The capacitated transshipment location problem with stochastic handling utilities at the facilities
Authors: Tadei Roberto , Perboli Guido , Ricciardi Nicoletta , Baldi Mauro Maria 
Published: April 2012

AbstractThe problem consists in finding a transshipment facilities location that maximizes the total net utility when the handling utilities at the facilities are stochastic variables, under supply, demand, and lower and upper capacity constraints. The total net utility is given by the expected total shipping utility minus the total fixed cost of the located facilities. Shipping utilities are given by a deterministic utility for shipping freight from origins to destinations via transshipment facilities plus a stochastic handling utility at the facilities, whose probability distribution is unknown. After giving the stochastic model, by means of some results of the extreme values theory, the probability distribution of the maximum stochastic utilities is derived and the expected value of the optimum of the stochastic model is found. An efficient heuristics for solving real‐life instances is also given. Computational results show a very good performance of the proposed methods both in terms of accuracy and efficiency.
Both α1‐ and β1‐adrenoceptors in the bed nucleus of the stria terminalis are involved in the expression of conditioned contextual fear
Authors: Hott Sara C , Gomes Felipe V , Fabri Denise RS , Reis Daniel G , Crestani Carlos C , Côrrea Fernando MA , Resstel Leonardo BM 
Published: April 2012

BACKGROUND AND PURPOSEThe bed nucleus of the stria terminalis (BNST) is a limbic structure that is involved in the expression of conditioned contextual fear. Among the numerous neural inputs to the BNST, noradrenergic synaptic terminals are prominent and some evidence suggests an activation of this noradrenergic neurotransmission in the BNST during aversive situations. Here, we have investigated the involvement of the BNST noradrenergic system in the modulation of behavioural and autonomic responses induced by conditioned contextual fear in rats.EXPERIMENTAL APPROACHMale Wistar rats with cannulae bilaterally implanted into the BNST were submitted to a 10 min conditioning session (6 footshocks, 1.5 ma/ 3 s). Twenty‐four hours later freezing and autonomic responses (mean arterial pressure, heart rate and cutaneous temperature) to the conditioning box were measured for 10 min. The adrenoceptor antagonists were administered 10 min before the re‐exposure to the aversive context.KEY RESULTSL‐propranolol, a non‐selective β‐adrenoceptor antagonist, and phentolamine, a non‐selective α‐adrenoceptor antagonist, reduced both freezing and autonomic responses induced by aversive context. Similar results were observed with CGP20712, a selective β1‐adrenoceptor antagonist, and WB4101, a selective α1‐antagonist, but not with ICI118,551, a selective β2‐adrenoceptor antagonist or RX821002, a selective α2‐antagonist.CONCLUSIONS AND IMPLICATIONSThese findings support the idea that noradrenergic neurotransmission in the BNST via α1‐ and β1‐adrenoceptors is involved in the expression of conditioned contextual fear.
Positive allosteric modulation by ivermectin of human but not murine P2X7 receptors
Authors: Nörenberg W , Sobottka H , Hempel C , Plötz T , Fischer W , Schmalzing G , Schaefer M 
Published: April 2012

BACKGROUND AND PURPOSEIn mammalian cells, the anti‐parasitic drug ivermectin is known as a positive allosteric modulator of the ATP‐activated ion channel P2X4 and is used to discriminate between P2X4‐ and P2X7‐mediated cellular responses. In this paper we provide evidence that the reported isoform selectivity of ivermectin is a species‐specific phenomenon.EXPERIMENTAL APPROACHComplementary electrophysiological and fluorometric methods were applied to evaluate the effect of ivermectin on recombinantly expressed and on native P2X7 receptors. A biophysical characterization of ionic currents and of the pore dilation properties is provided.KEY RESULTSUnexpectedly, ivermectin potentiated currents in human monocyte‐derived macrophages that endogenously express hP2X7 receptors. Likewise, currents and [Ca2+]i influx through recombinant human (hP2X7) receptors were potently enhanced by ivermectin at submaximal or saturating ATP concentrations. Since intracellular ivermectin did not mimic or prevent its activity when applied to the bath solution, the binding site of ivermectin on hP2X7 receptors appears to be accessible from the extracellular side. In contrast to currents through P2X4 receptors, ivermectin did not cause a delay in hP2X7 current decay upon ATP removal. Interestingly, NMDG+ permeability and Yo‐Pro‐1 uptake were not affected by ivermectin. On rat or mouse P2X7 receptors, ivermectin was only poorly effective, suggesting a species‐specific mode of action.CONCLUSIONS AND IMPLICATIONSThe data indicate a previously unrecognized species‐specific modulation of human P2X7 receptors by ivermectin that should be considered when using this cell‐biological tool in human cells and tissues.
Augmentation of cognitive function by NS9283, a stoichiometry‐dependent positive allosteric modulator of α2‐ and α4‐containing nicotinic acetylcholine receptors
Authors: Timmermann DB , Sandager‐Nielsen K , Dyhring T , Smith M , Jacobsen A‐M , Nielsen EØ , Grunnet M , Christensen JK , Peters D , Kohlhaas K , Olsen GM , Ahring PK 
Published: April 2012

BACKGROUND AND PURPOSEPositive allosteric modulation of α4β2 nicotinic acetylcholine (nACh) receptors could add a new dimension to the pharmacology and therapeutic approach to these receptors. The novel modulator NS9283 was therefore tested extensively.EXPERIMENTAL APPROACHEffects of NS9283 were evaluated in vitro using fluorescence‐based Ca2+ imaging and electrophysiological voltage clamp experiments in Xenopus oocytes, mammalian cells and thalamocortical neurons. In vivo the compound was tested in models covering a range of cognitive domains in mice and rats.KEY RESULTSNS9283 was shown to increase agonist‐evoked response amplitude of (α4)3(β2)2 nACh receptors in electrophysiology paradigms. (α2)3(β2)2, (α2)3(β4)2 and (α4)3(β4)2 were modulated to comparable extents, but no effects were detected at α3‐containing or any 2α : 3β stoichiometry nACh receptors. Native nACh receptors in thalamocortical neurons similarly displayed DHβE‐sensitive currents that were receptive to modulation. NS9283 had favourable effects on sensory information processing, as shown by reversal of PCP‐disrupted pre‐pulse inhibition. NS9283 further improved performance in a rat model of episodic memory (social recognition), a rat model of sustained attention (five‐choice serial reaction time task) and a rat model of reference memory (Morris water maze). Importantly, the effects in the Morris water maze could be fully reversed with mecamylamine, a blocker of nACh receptors.CONCLUSIONS AND IMPLICATIONSThese results provide compelling evidence that positive allosteric modulators acting at the (α4)3(β2)2 nACh receptors can augment activity across a broad range of cognitive domains, and that α4β2 nACh receptor allosteric modulation therefore constitutes a promising therapeutic approach to symptomatic treatment of cognitive impairment.
The struggle for reform: contested conceptualizations of iṣlāḥ in the Maghreb*
Authors: Macías Amoretti Juan A. , Fuentes Juan Marsá 
Published: April 2012

AbstractThis contribution draws an historical and conceptual analysis of the concept of iṣlāḥ, which is traditionally understood as “reform” in general terms, and tries to stress the origins and the main conceptual paradigms of the two main ideological and political lines in which this concept has been developed and is still used in the Arab Maghreb by main political actors and thinkers.
Anti‐fibrotic activity and enhanced interleukin‐6 production by hepatic stellate cells in response to imatinib mesylate
Authors: Kim Youngchul , Fiel Maria I. , Albanis Efsevia , Chou Hsin I. , Zhang Weijia , Khitrov Gregory , Friedman Scott L. 
Published: April 2012

AbstractObjectiveTo examine imatinib mesylate's effects on stellate cell responses in vivo and in vitro. The hepatic stellate cell (HSC) is a key target of anti‐fibrotic therapies. Imatinib mesylate is a small molecule receptor tyrosine kinase inhibitor indicated for treatment of chronic myelogenous leukaemia and GI stromal tumours.DesignBecause imatinib inhibits β‐PDGFR signalling, which stimulates HSC proliferation, we assessed its activity in culture and in vivo, and examined downstream targets in a human stellate cell line (LX‐2) using cDNA microarray.Methods and ResultsImatinib inhibited proliferation of LX‐2 cells (0.5–10 mM) but not primary human stellate cells, with no effect on viability, associated with attenuated β‐PDGFR phosphorylation. Mitochondrial activity and superoxide anion production were decreased in response to imatinib. cDNA microarray uncovered up‐regulation of 29 genes in response to imatinib, including interleukin‐6 (IL‐6) mRNA, which was correlated with progressive IL‐6 secretion. Imatinib also decreased gene expression of collagen α1(I), alpha smooth muscle actin, β‐PDGFR, transforming growth factor β receptor type 1, matrix metalloproteinase 2 and tissue inhibitor of metalloproteinase 2. In vivo, imatinib administered to rats beginning 4 weeks after starting thioacetamide (TAA) led to reduced collagen content, with significant reductions in portal pressure and down‐regulation of fibrogenic genes in whole liver. Importantly, hepatic IL‐6 mRNA levels were significantly increased in TAA‐treated animals receiving imatinib.ConclusionsThese findings reinforce the anti‐fibrotic activity of imatinib and uncover an unexpected link between inhibition of HSC activation by imatinib and enhanced secretion of IL‐6, a regenerative cytokine.
Postoperative adverse outcomes in surgical patients with epilepsy: A population‐based study
Authors: Chang Chuen‐Chau , Hu Chaur‐Jong , Lam Fai , Chang Hang , Liao Chien‐Chang , Chen Ta‐Liang 
Published: April 2012

SummaryPurpose:  People with epilepsy are more likely than healthy people to experience comorbidities and complications in various medical situations. However, the prevalence of postoperative complications, mortality, and use of medical resources in surgical patients with epilepsy has not been studied. The purpose of this study is to examine whether epilepsy is an independent risk factor for postoperative adverse outcomes of patients receiving major surgery.Methods:  Retrospective cohort study using the National Health Insurance Research Database to identify patients with epilepsy who underwent major surgery in Taiwan between the years 2004 and 2007. For each case, four age‐ and sex‐matched participants without epilepsy were included. Preoperative comorbidities in the 24 months before surgery were identified. Eight major postoperative complications, overall 30‐day mortality, and in‐hospital utilization of medical resources (including length of hospital stay, percentage of postoperative intensive care unit admissions, and in‐hospital medical expenditures) served as the major outcome measurements. Comorbidities, status of receiving renal dialysis, teaching hospital status, types of surgery, and patients living in urban or rural areas were adjusted by multivariate logistic regression.Key Findings:  A total of 13,103 participants with epilepsy and 52,412 without were included. Patients with epilepsy have significantly more preoperative comorbidities and demonstrated more risks of any postoperative complications (odds ratio 2.02, 95% confidence interval 1.90–2.14). Consumption of in‐hospital medical resources was also significantly higher in patients with epilepsy, but no significant differences in postoperative mortality rates between the two groups were noted.Significance:  Stroke was identified as the most significant postoperative complication for surgical patients with epilepsy. Patients, especially those with previous hospitalization or emergency visits due to the disease, confronted significantly higher postoperative complication rates, and consumed more in‐hospital medical resources without differences in overall mortality rates. Further revision of health care standards to provide early recognition of postoperative complications and better management for surgical patients with epilepsy is needed.
The role of voxel‐based morphometry in the detection of cortical dysplasia within the temporal pole in patients with intractable mesial temporal lobe epilepsy
Authors: Pail Martin , Mareček Radek , Hermanová Markéta , Slaná Bronislava , Tyrlíková Ivana , Kuba Robert , Brázdil Milan 
Published: April 2012

SummaryPurpose:  To determine whether voxel‐based morphometry (VBM) might contribute to the detection of cortical dysplasia within the temporal pole in patients with mesial temporal lobe epilepsy and hippocampal sclerosis (MTLE/HS).Methods:  Eighteen patients with intractable MTLE/HS and 30 sex‐ and age‐matched healthy controls were included in the study. All of the patients fulfilled the diagnostic criteria for MTLE/HS and underwent anteromedial temporal resection. VBM without a modulation step was applied to the magnetic resonance (MR) images of the brain. Statistical parametric maps were used to compare structural characteristics such as gray matter concentration (GMC) within the temporal pole among patients and controls separately. The acquired data were then statistically analyzed to determine the congruency between visually inspected MR imaging (MRI) scans and VBM results in the detection of morphologic abnormalities in the temporal pole compared to postoperative histopathologic findings of cortical dysplasia.Key Findings:  Histopathologic examination revealed cortical dysplasia within the temporal pole in 11 patients. In detail, according to Palmini’s classification, mild malformations of cortical development (mMCDs) were disclosed in three patients, focal cortical dysplasia (FCD) type Ia in three patients, and FCD type Ib in five patients. Some type of structural temporal pole abnormality was suggested by VBM in 14 patients and by visually inspected MRI scans in 11 patients. The results of VBM were in agreement with the presence/absence of cortical dysplasia in 13 patients (72.2%); this correspondence was significant (p = 0.047). In one case, VBM was false negative and in four cases it was false positive. There was congruence between the results of visual analysis and histologic proof in 55.6% of examined patients, which was not significant.Significance:  We found that VBM made a superior contribution to the detection of temporopolar structural malformations (cortical dysplasia) compared to visual inspection. The agreement with postoperative histopathologic proof was clearly significant for VBM results and nonsignificant for visual inspection.
Youth Recovery Contexts: The Incremental Effects of 12‐Step Attendance and Involvement on Adolescent Outpatient Outcomes
Authors: Kelly John F. , Urbanoski Karen 
Published: April 2012

BackgroundA major barrier to youth recovery is finding suitable sobriety‐supportive social contexts. National studies reveal most adolescent addiction treatment programs link youths to community 12‐step fellowships to help meet this challenge, but little is known empirically regarding the extent to which adolescents attend and benefit from 12‐step meetings or whether they derive additional gains from active involvement in prescribed 12‐step activities (e.g., contact with a sponsor and other fellowship members). Greater knowledge in this area would enhance the efficiency of clinical continuing care recommendations.MethodsAdolescent outpatients (N = 127; M age 16.7; 75% male; 87% white) enrolled in a naturalistic study of treatment effectiveness were assessed at intake and 3, 6, and 12 months later using standardized assessments. Mixed‐effects models, controlling for static and time‐varying confounds, examined the concurrent and lagged effects of 12‐step attendance and active involvement on abstinence over time.ResultsThe proportion attending 12‐step meetings was relatively low across follow‐up (24 to 29%), but more frequent attendance was independently associated with greater abstinence in concurrent and, to a lesser extent, lagged models. An 8‐item composite measure of 12‐step involvement did not enhance outcomes over and above attendance, but separate components did; specifically, greater contact with a 12‐step sponsor outside of meetings and more verbal participation during meetings.ConclusionsThe benefits of 12‐step participation observed among adult samples extend to adolescent outpatients. Community 12‐step fellowships appear to provide a useful sobriety‐supportive social context for youths seeking recovery, but evidence‐based youth‐specific 12‐step facilitation strategies are needed to enhance outpatient attendance rates.