bluuebunny/crossref_metadata_2025_split huggingface dataset:
Redox‐based endoplasmic reticulum dysfunction in neurological diseases
Authors: Bánhegyi Gábor , Mandl József , Csala Miklós 
Published: July 2008

AbstractThe redox homeostasis of the endoplasmic reticulum lumen is characteristically different from that of the other subcellular compartments. The concerted action of membrane transport processes and oxidoreductase enzymes maintain the oxidized state of the thiol‐disulfide and the reducing state of the pyridine nucleotide redox systems, which are prerequisites for the normal functions of the organelle. The powerful thiol‐oxidizing machinery allows oxidative protein folding but continuously challenges the local antioxidant defense. Alterations of the cellular redox environment either in oxidizing or reducing direction affect protein processing and may induce endoplasmic reticulum stress and unfolded protein response. The activated signaling pathways attempt to restore the balance between protein loading and processing and induce apoptosis if the attempt fails. Recent findings strongly support the involvement of this mechanism in brain ischemia, neuronal degenerative diseases and traumatic injury. The redox changes in the endoplasmic reticulum are integral parts of the pathomechanism of neurological diseases, either as causative agents, or as complications.
Dopamine is necessary to endogenous morphine formation in mammalian brain in vivo
Authors: Neri Carla , Ghelardini Carla , Sotak Bethany , Palmiter Richard D. , Guarna Massimo , Stefano George , Bianchi Enrica 
Published: July 2008

AbstractMorphine, the most used compound among narcotic analgesics, has been shown to be endogenously present in different mammalian/invertebrate normal tissues. In this study, we used mice that cannot make dopamine due to a genetic deletion of tyrosine hydroxylase specifically in dopaminergic neurons, to test the hypothesis that endogenous dopamine is necessary to endogenous morphine formation in vivo in mammalian brain. When dopamine was lacking in brain neurons, endogenous morphine was missing in brain mouse whereas it could be detected in brain from wild type rodent at a picogram range. Our data prove for the first time that endogenous dopamine is necessary to endogenous morphine formation in normal mammalian brain. Morphine synthesis appears to be originated from dopamine through L‐tyrosine in normal brain tissue. Morphine synthesis is not considered to occur inside the same neuron in normal tissue; released dopamine might be transported into morphinergic neuron and further transformed into morphine. A physiological role for endogenous morphine is suggested considering that dopamine could modulate thermal threshold through endogenous morphine formation in vivo. Thus, dopamine and endogenous opiates/opioid peptides may be interconnected in the physiological processes; yet, endogenous morphine may represent a basic link of this chain.
Edaravone protects against MPP+‐induced cytotoxicity in rat primary cultured astrocytes via inhibition of mitochondrial apoptotic pathway
Authors: Chen Hui , Wang Sen , Ding Jian‐Hua , Hu Gang 
Published: July 2008

AbstractEdaravone (Eda) is a potent scavenger of hydroxyl radicals and has been demonstrated to be beneficial for patients with acute ischemic stroke. This study was set out to investigate whether Eda protect against MPP+‐induced cytotoxicity in rat primary cultured astrocytes. The results showed that pre‐treatment with Eda inhibited astrocytic apoptosis and lactate dehydrogenase release induced by MPP+ (200 μM). Further study revealed that Eda prevented GSH depletion, down‐regulated mRNA expressions of NADPH oxidase membrane subunit gp91 and membrane‐translocated subunit p47, and prevented the decreases of state 3 respiration respiration and respiratory control ratio induced by MPP+, and thereby inhibited reactive oxygen species production evoked by MPP+. Moreover, Eda could ameliorate mitochondrial respiratory function, restrain, and prevent mitochondrial membrane potential loss induced by MPP+. Consequently, Eda inhibited releases of cytochrome c and apoptosis‐inducing factor induced by MPP+. Taken together, these findings reveal for the first time that Eda protects against MPP+‐induced astrocytic apoptosis via decreasing intracellular reactive oxygen species level and subsequently inhibiting mitochondrial apoptotic pathway. The antiapoptosis effects of Eda on astrocytes may provide a new perspective on neuroprotective therapy.
Covalent modification of GABAAreceptor isoforms by a diazepam analogue provides evidence for a novel benzodiazepine binding site that prevents modulation by these drugs
Authors: Baur Roland , Tan Kelly R. , Lüscher Benjamin P. , Gonthier Anne , Goeldner Maurice , Sigel Erwin 
Published: July 2008

AbstractClassical benzodiazepines, for example diazepam, interact with αxβ2γ2GABAAreceptors, x = 1, 2, 3, 5. Little is known about effects of α subunits on the structure of the binding pocket. We studied here the interaction of the covalently reacting diazepam analog 7‐Isothiocyanato‐5‐phenyl‐1,3‐dihydro‐2H‐1,4‐benzodiazepin‐2‐one (NCS compound) with α1H101Cβ2γ2and with receptors containing the homologous mutation, α2H101Cβ2γ2, α3H126Cβ2γ2and α5H105Cβ2γ2. This comparison was extended to α6R100Cβ2γ2receptors as this mutation conveys to these receptors high affinity towards classical benzodiazepines. The interaction was studied at the ligand binding level and at the functional level using electrophysiological techniques. Results indicate that the geometry of α6R100Cβ2γ2enables best interaction with NCS compound, followed by α3H126Cβ2γ2, α1H101Cβ2γ2and α2H101Cβ2γ2, while α5H105Cβ2γ2receptors show little interaction. Our results allow conclusions about the relative apposition of α1H101 and homologous positions in α2, α3, α5and α6with the position occupied by –Cl in diazepam. During this study we found evidence for the presence of a novel site for benzodiazepines that prevents modulation of GABAAreceptors via the classical benzodiazepine site. The novel site potentially contributes to the high degree of safety to some of these drugs. Our results indicate that this site may be located at the α/β subunit interface pseudo‐symmetrically to the site for classical benzodiazepines located at the α/γ interface.
Chromatin immunoprecipitation scanning identifies glucocorticoid receptor binding regions in the proximal promoter of a ubiquitously expressed glucocorticoid target gene in brain
Authors: Van Der Laan Siem , Sarabdjitsingh R. Angela , Van Batenburg Marcel F. , Lachize Servane B. , Li Hualing , Dijkmans Thomas F. , Vreugdenhil Erno , De Kloet E. Ron , Meijer Onno C. 
Published: July 2008

AbstractWhile the actions of glucocorticoids on brain functions have been comprehensively studied, the underlying genomic mechanisms are poorly understood. In this study, we show that glucocorticoid‐induced leucine zipper (GILZ) mRNA is strongly and ubiquitously induced in rat brain. To decipher the molecular mechanisms underlying these genomic effects, it is of interest to identify the regulatory sites in the promoter region. Alignment of the rat GILZ promoter with the well‐characterized human promoter resulted in poor sequence homology. Consequently, we analyzed the rat 5′ flanking sequence by Matrix REDUCE and identified two high‐affinity glucocorticoid response elements (GRE) located 2 kb upstream of the transcription start site. These findings were corroborated using the glucocorticoid receptor (GR) expressing Ns‐1 PC12 rat cell‐line. In these cells, dexamethasone treatment leads to a progressive increase of GILZ mRNA expression levels via a GR‐dependent mechanism. Subsequently, using chromatin immunoprecipitation assays we show that the two high‐affinity GREs are located within the GR‐binding regions. Lastly, we demonstrate using multiple tissue in situ hybridization a marked increase in mRNA expression levels in spleen, thymus, heart, lung, liver, muscle, testis, kidney, colon, ileum, as well as in brain and conclude that the GILZ gene can be used to study glucocorticoid effects in many additional rodent tissues.
Mechanisms of hyperthermia‐induced depression of GABAergic synaptic transmission in the immature rat hippocampus
Authors: Qu Lintao , Leung L. Stan 
Published: July 2008

AbstractClinical observations and experimental studies have shown that hyperthermia can provoke febrile seizures, which are the most common type of pathological brain activity in children. We previously demonstrated that hyperthermia produced a depression of GABAergic neurotransmission in the hippocampus of immature ratsin vitro. To investigate the possible mechanisms through which hyperthermia may modulate GABAergic neurotransmission in the hippocampus, whole‐cell voltage clamp recordings were performed on CA1 pyramidal neurons in the immature rat brain slices. We found that hyperthermia (38.4–40°C) when compared with baseline temperature of 32°C reduced the frequency of both spontaneous inhibitory post‐synaptic currents (sIPSCs) and miniature IPSCs (mIPSCs). Also, hyperthermia decreased the amplitudes of mIPSCs and reduced the mIPSC decay time constants and charge transfer. Non‐stationary noise analysis of mIPSCs suggested that the number of open post‐synaptic receptors but not single channel conductance was reduced during hyperthermia. Activation of adenylyl cyclase with forskolin prevented, whereas protein kinase A inhibitorN‐(2‐[p‐bromocinnamylamino]ethyl)‐5‐isoquinolinesulfonamide potentiated, the hyperthermia (40°C)‐induced depression of evoked IPSCs (evIPSCs). But protein kinase C activator phorbol 12, 13‐dibutyrate (PDBu) did not significantly affect this depression of evIPSCs induced by hyperthermia. Furthermore, hyperthermia‐induced depression of evIPSCs was attenuated by 4‐aminopyridine, but not by BaCl2. These results suggest that hyperthermia reduces GABA release from pre‐synaptic terminals, in part by blocking the adenylyl cyclase–protein kinase A signaling pathway and activating pre‐synaptic 4‐aminopyridine‐sensitive K+channels. Also, the changes in amplitude and decay time constant of the mIPSCs may suggest that hyperthermia also decreases post‐synaptic GABAAreceptor function.
Healthcare Cost Differences with Participation in a Community‐Based Group Physical Activity Benefit for Medicare Managed Care Health Plan Members
Authors: Ackermann Ronald T. , Williams Barbara , Nguyen Huong Q. , Berke Ethan M. , Maciejewski Matthew L. , LoGerfo James P. 
Published: July 2008

OBJECTIVES: To determine whether participation in a physical activity benefit by Medicare managed care enrollees is associated with lower healthcare utilization and costs.DESIGN: Retrospective cohort study.SETTING: Medicare managed care.PARTICIPANTS: A cohort of 1,188 older adult health maintenance organization enrollees who participated at least once in the EnhanceFitness (EF) physical activity benefit and a matched group of enrollees who never used the program.MEASUREMENTS: Healthcare costs and utilization were estimated. Ordinary least squares regression was used, adjusting for demographics, comorbidity, indicators of preventive service use, and baseline utilization or cost. Robustness of findings was tested in sensitivity analyses involving continuous propensity score adjustment and generalized linear models with nonconstant variance assumptions.RESULTS: EF participants had similar total healthcare costs during Year 1 of the program, but during Year 2, adjusted total costs were $1,186 lower (P=.005) than for non‐EF users. Differences were partially attributable to lower inpatient costs (−$3,384; P=.02), which did not result from high‐cost outliers. Enrollees who attended EF an average of one visit or more per week had lower adjusted total healthcare costs in Year 1 (−$1,929; P<.001) and Year 2 (−$1,784; P<.001) than nonusers.CONCLUSION: Health plan coverage of a preventive physical activity benefit for seniors is a promising strategy to avoid significant healthcare costs in the short term.
The Sacramentality of Things
Authors: Sherry Patrick 
Published: July 2008

AbstractI discuss the recent tendency to extend the concept of sacramentality by applying it to the world or to aspects of it like beauty, e.g. by David Brown in his God and the Enchantment of Place. I look at the Church's traditional teaching on sacraments, in terms of signs, words, and effectiveness, making use of J.L.Austin's work on Performative Utterances, and explore how these three features might apply to the extended concept of a sacrament. I argue that we can perceive signs-by-likeness of God in the world, especially in beauty, and that we can often discern the effectiveness of such signs. We lack, however, anything here corresponding to the words of the sacraments of the Church. I conclude, therefore, that the parallel between sacraments in an extended sense and the sacraments of the Church is only partial; nevertheless the extended usage is justifiable, provided that we realize its limitations.
Novel Nuclear Protein ALC‐INTERACTING PROTEIN1 is Expressed in Vascular and Mesocarp Cells inArabidopsis
Authors: Wang Fang , Shi Dong‐Qiao , Liu Jie , Yang Wei‐Cai 
Published: July 2008

AbstractPod shattering is an agronomical trait that is a result of the coordinated action of cell differentiation and separation. InArabidopsis, pod shattering is controlled by a complex genetic network in which ALCATRAZ (ALC), a member of the basic helix‐loop‐helix family, is critical for cell separation during fruit dehiscence. Herein, we report the identification of ALC‐INTERACTING PROTEIN1 (ACI1) via the yeast two‐hybrid screen.ACI1encodes a nuclear protein with a lysine‐rich domain and a C‐terminal serine‐rich domain.ACI1is mainly expressed in the vascular system throughout the plant and mesocarp of the valve in siliques. Our data showed that ACI1 interacts strongly with the N‐terminal portion of ALC in yeast cells and in plant cells in the nucleus as demonstrated by bimolecular fluorescence complementation assay. BothACI1andALCshare an overlapping expression pattern, suggesting that they likely function together in planta. However, no detectable phenotype was found in plants with reducedACI1expression by RNA interference technology, suggesting thatACI1may be redundant. Taken together, these data indicate that ALC may interact with ACI1 and its homologs to control cell separation during fruit dehiscence inArabidopsis.
Perspectives in Biological Nitrogen Fixation Research
Authors: Cheng Qi 
Published: July 2008

Abstract Nitrogen fixation, along with photosynthesis is the basis of all life on earth. Current understanding suggests that no plant fixes its own nitrogen. Some plants (mainly legumes) fix nitrogen via symbiotic anaerobic microorganisms (mainly rhizobia). The nature of biological nitrogen fixation is that the dinitrogenase catalyzes the reaction‐splitting triple‐bond inert atmospheric nitrogen (N2) into organic ammonia molecule (NH3). All known nitrogenases are found to be prokaryotic, multi‐complex and normally oxygen liable. Not surprisingly, the engineering of autonomous nitrogen‐fixing plants would be a long‐term effort because it requires the assembly of a complex enzyme and provision of anaerobic conditions. However, in the light of evolving protein catalysts, the anaerobic enzyme has almost certainly been replaced in many reactions by the more efficient and irreversible aerobic version that uses O2. On the other hand, nature has shown numerous examples of evolutionary convergence where an enzyme catalyzing a highly specific, O2‐requiring reaction has an oxygen‐independent counterpart, able to carry out the same reaction under anoxic conditions. In this review, I attempt to take the reader on a simplified journey from conventional nitrogenase complex to a possible simplified version of a yet to be discovered light‐utilizing nitrogenase.
Cell Fate Switch during In Vitro Plant Organogenesis
Authors: Zhao Xiang Yu , Su Ying Hua , Cheng Zhi Juan , Zhang Xian Sheng 
Published: July 2008

Abstract Plant mature cells have the capability to reverse their state of differentiation and produce new organs under cultured conditions. Two phases, dedifferentiation and redifferentiation, are commonly characterized during in vitro organogenesis. In these processes, cells undergo fate switch several times regulated by both extrinsic and intrinsic factors, which are associated with reentry to the cell cycle, the balance between euchromatin and heterochromatin, reprogramming of gene expression, and so forth. This short article reviews the advances in the mechanism of organ regeneration from plant somatic cells in molecular, genomic and epigenetic aspects, aiming to provide important information on the mechanism underlying cell fate switch during in vitro plant organogenesis.
Signaling in Plant Disease Resistance and Symbiosis
Authors: Zhao Songzi , Qi Xiaoquan 
Published: July 2008

Abstract Interactions between plants and microbes result in plant disease and symbiosis. The former causes considerable economic damage in modern agriculture, while the latter has produced great beneficial effects to our agriculture system. Comparison of the two interactions has revealed that a common panel of signaling pathways might participate in the establishment of the equilibrium between plant and microbes or its break‐up. Plants appear to detect both pathogenic and symbiotic microbes by a similar set of genes. All symbiotic microbes seem to produce effectors to overcome plant basal defenses and it is speculated that symbiotic effectors have functions similar to pathogenic ones. Signaling molecules, salicylic acid (SA), jasmonic acid (JA) and ethylene (ET), are involved in both plant defense and symbiosis. Switching off signals contributing to deterioration of disease symptom would establish a new equilibrium between plant and pathogenic microbes. This would facilitate the development of strategies for durable disease resistance.
Evolutionarily Conserved DELLA‐mediated Gibberellin Signaling in Plants
Authors: Gao Xiu‐Hua , Huang Xian‐Zhong , Xiao Sen‐Lin , Fu Xiang‐Dong 
Published: July 2008

Abstract Gibberellins (GAs) play important roles in many essential plant growth and development processes. A family of nuclear growth‐repressing DELLA proteins is the key component in GA signaling. GA perception is mediated by GID1, and the key event of GA signaling is the degradation of DELLA proteins via the 26S proteasome pathway. DELLA proteins integrating other plant hormones signaling and environmental cue modulating plant growth and development have been revealed. GA turning on the de‐DELLA‐repressing system is conserved, and independently establishes step‐by‐step recruitment of GA‐stimulated GID1‐DELLA interaction and DELLA growth‐repression functions during land plant evolution. These discoveries open new prospects for the understanding of GA action and DELLA‐mediated signaling in plants.
Histone Deacetylase Genes in Arabidopsis Development
Authors: Hollender Courtney , Liu Zhongchi 
Published: July 2008

Abstract Histone acetylation and deacetylation are directly connected with transcriptional activation and silencing in eukaryotes. Gene families for enzymes that accomplish these histone modifications show surprising complexity in domain organization, tissue‐specific expression, and function. This review is focused on the family of histone deacetylases (HDACs) that remove the acetyl group from core histone tails, resulting in a “closed” chromatin and transcriptional repression. In Arabidopsis, 18 HDAC genes are divided into three different types – RPD3‐like, HD‐tuin and sirtuin – with two or more members in each type. The structural feature of each HDAC class, the expression profile of each HDAC gene during development and functional insights of important family members are summarized here. It is clear that HDACs are an important class of global transcriptional regulators that play crucial roles in plant development, defense, and adaptation.
Sexual Reproduction in Higher Plants I: Fertilization and the Initiation of Zygotic Program
Authors: Fan Yong‐Feng , Jiang Li , Gong Hua‐Qin , Liu Chun‐Ming 
Published: July 2008

Abstract Sexual plant reproduction is a critical developmental step in the life cycle of higher plants, to allow maternal and paternal genes to be transmitted in a highly regulated manner to the next generation. During evolution, a whole set of signal transduction machinery is developed by plants to ensure an error‐free recognition between male and female gametes and initiation of zygotic program. In the past few years, the molecular machineries underlying this biological process have been elucidated, particularly on the importance of synergid cells in pollen tube guidance, the Ca++ spike as the immediate response of fertilization and the epigenetic regulation of parental gene expressions in early zygotic embryogenesis. This review outlines the most recent development in this area.
Carotenoid Metabolism: Biosynthesis, Regulation, and Beyond
Authors: Lu Shan , Li Li 
Published: July 2008

Abstract Carotenoids are indispensable to plants and play a critical role in human nutrition and health. Significant progress has been made in our understanding of carotenoid metabolism in plants. The biosynthetic pathway has been extensively studied. Nearly all the genes encoding the biosynthetic enzymes have been isolated and characterized from various organisms. In recent years, there is an increasing body of work on the signaling pathways and plastid development, which might provide global control of carotenoid biosynthesis and accumulation. Herein, we will highlight recent progress on the biosynthesis, regulation, and metabolic engineering of carotenoids in plants, as well as the future research towards elucidating the regulatory mechanisms and metabolic network that control carotenoid metabolism.
Genetic Basis of Ethylene Perception and Signal Transduction in Arabidopsis
Authors: Zhu Ziqiang , Guo Hongwei 
Published: July 2008

Abstract Ethylene is a simple gaseous hormone in plants. It plays important roles in plant development and stress tolerance. In the presence of ethylene treatment, all ethylene receptors are in an activated form, which can physically interact with CTR1 and consequently recruit CTR1 protein to endoplasmic reticulum membrane
to activate it. Activated CTR1 suppresses the downstream signal transduction by an unknown mechanism. Upon binding to its receptors, ethylene will inactivate the receptor/CTR1 module and in turn alleviate their inhibitory effect on two positive regulators acting downstream of CTR1: EIN2 and EIN3. Genetic study reveals that EIN2 is an essential component in the ethylene signaling pathway but its biochemical function remains a mystery. EIN3 is a plant‐specific transcription factor and its protein abundance in the nucleus is rapidly induced upon ethylene treatment. In the absence of ethylene signal, EIN3 protein is degraded by an SCF complex containing one of the two F‐box proteins EBF1/EBF2 in a 26S proteasome‐dependent manner. EIN3 can bind to the promoter sequences of a number of downstream components, such as ERFs, which in turn bind to a GCC box, a cis‐element found in many ethylene‐regulated defense genes. Ethylene has been shown to also regulate many other hormones' signaling pathways including auxin, abscisic acid and jasmonic acid, implying the existence of complicated signaling networks in the growth, development and defense responses of various plants.