bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adenosine and sleep deprivation promote NF‐κB nuclear translocation in cholinergic basal forebrain
Authors: Ramesh Vijay , Thatte Hemant S. , McCarley Robert W. , Basheer Radhika 
Published: January 2007

AbstractIn our investigations related to the homeostatic sleep factor adenosine (AD), we previously demonstrated that the DNA‐binding activity of the transcription factor NF‐κB in rat cholinergic basal forebrain increased following 3 h of sleep deprivation (SD). However, the neurotransmitter nature of the cells and the SD‐induced stimuli responsible for NF‐κB activation were not defined. In this report, we demonstrate, using double labeling immunohistochemistry, that nuclear translocation of NF‐κB occurs almost exclusively in the cholinergic neurons of the basal forebrain following 3 h of SD. Furthermore, cholinergic basal forebrain microinjection of AD (25 nmol/L) or the A1 receptor agonist N6‐cyclo‐hexyladenosine (100 nmol/L) induced nuclear translocation of NF‐κB, thus suggesting that SD‐induced increased extracellular concentrations of AD, acting via the A1 AD receptor, may be responsible for the nuclear translocation of NF‐κB in cholinergic neurons. Moreover, blocking the nuclear translocation of NF‐κB by injection of inhibitor peptide, SN50, immediately prior to 6 h SD significantly reduced delta activity (1–4 Hz) during the first two hours of recovery sleep. Together, these data suggest a role in sleep homeostasis for the SD‐induced activation of NF‐κB in cholinergic basal forebrain, and that transcription factor NF‐κB may code for factor(s) that play a role in sleep homeostasis.
Hypoxia‐like transcriptional activation in TMT‐induced degeneration: microarray expression analysis on PC12 cells
Authors: Lattanzi Wanda , Bernardini Camilla , Gangitano Carlo , Michetti Fabrizio 
Published: January 2007

AbstractTo more clearly elucidate the complete network of molecular mechanisms induced by trimethyltin (TMT) toxicity, we used a homogeneous cell culture model represented by PC12 cells treated with 1 and 5 μmol/L TMT for 24 h. The gene expression profile was performed by microarray analysis, enabling us to identify 189 genes that were significantly modulated in treated cells, compared with controls. The main effects of TMT on gene expression seem to be related to the activation of metabolic processes (glycolysis and lipogenesis) along with cell death pathways, membrane remodeling and intracellular biomolecules trafficking. These alterations are triggered by the neurotoxicant earlier than a strong decrease in cell viability, which occurs at higher TMT concentrations or at later time points. Some aspects of the transcriptional modulation observed in this study resemble the gene activation known to occur during cell response to hypoxia. Other cell toxicants have also been reported to exert similar effects on gene expression. Therefore, our data help to delineate general basic adaptive mechanisms possibly shared by cells responding to different death‐inducing noxae, such as TMT.
Differential role of extracellular histidines in copper, zinc, magnesium and proton modulation of the P2X7 purinergic receptor
Authors: Acuña‐Castillo Claudio , Coddou Claudio , Bull Paulina , Brito Jocelyn , Huidobro‐Toro J. Pablo 
Published: January 2007

AbstractThe P2X7 receptor is a non‐selective cationic channel activated by extracellular ATP, belonging to the P2X receptor family. To assess the role of extracellular histidines on the allosteric modulation of the rat P2X7 receptor by divalent metals (copper, zinc and magnesium) and protons, these amino acid residues were singly substituted for corresponding alanines. Wild‐type and mutated receptors were injected to Xenopus laevis oocytes; metal‐related effects were evaluated by the two‐electrode voltage‐clamp technique. Copper inhibited the ATP‐gated currents with a median inhibitory concentration of 4.4 ± 1.0 µmol/L. The inhibition was non‐competitive and time‐dependent; copper was 60‐fold more potent than zinc. The mutant H267A, resulted in a copper resistant receptor; mutants H201A and H130A were less sensitive to copper inhibition (p < 0.05). The rest of the mutants examined, H62A, H85A, and H219A, conserved the copper‐induced inhibition. Only mutants H267A and H219A were less sensitive to the modulator action of zinc. Moreover, the magnesium‐induced inhibition was abolished exclusively on the H130A and H201A mutants, suggesting that this metal may act at a novel cationic modulator site. Media acidification inhibited the ATP‐gated current 87 ± 3%; out of the six mutants examined, only H130A was significantly less sensitive to the change in pH, suggesting that His‐130 could be involved as a pH sensor. In conclusion, while His‐267 is critically involved in the copper or zinc allosteric modulation, the magnesium inhibitory effects is related to His‐130 and His‐201, His‐130 is involved in proton sensing, highlighting the role of defined extracellular histidines in rat P2X7 receptor allosteric modulation.
Mitochondrial dysfunction in Huntington’s disease: the bioenergetics of isolated and in situ mitochondria from transgenic mice
Authors: Oliveira Jorge M. A. , Jekabsons Mika B. , Chen Sylvia , Lin Amy , Rego A. Cristina , Gonçalves Jorge , Ellerby Lisa M. , Nicholls David G. 
Published: January 2007

AbstractMitochondrial dysfunction is believed to participate in Huntington’s disease (HD) pathogenesis. Here we compare the bioenergetic behavior of forebrain mitochondria isolated from different transgenic HD mice (R6/2, YAC128 and Hdh150 knock‐in) and wild‐type littermates with the first determination of in situ respiratory parameters in intact HD striatal neurons. We assess the Ca2+‐loading capacity of isolated mitochondria by steady Ca2+‐infusion. Mitochondria from R6/2 mice (12–13 weeks) and 12 months YAC128, but not homozygous or heterozygous Hdh150 knock‐in mice (15–17 weeks), exhibit increased Ca2+‐loading capacity when compared with respective wild‐type littermates. In situ mitochondria in intact striatal neurons show high respiratory control. Moreover, moderate expression of full‐length mutant huntingtin (in Hdh150 knock‐in heterozygotes) does not significantly impair mitochondrial respiration in unstimulated neurons. However, when challenged with energy‐demanding stimuli (NMDA‐receptor activation in pyruvate‐based media to accentuate the mitochondria role in Ca2+‐handling), Hdh150 neurons are more vulnerable to Ca2+‐deregulation than neurons from their wild‐type littermates. These results stress the importance of assessing HD mitochondrial function in the cellular context.
Peroxisome proliferator‐activated receptor‐γ agonists induce neuroprotection following transient focal ischemia in normotensive, normoglycemic as well as hypertensive and type‐2 diabetic rodents
Authors: Tureyen Kudret , Kapadia Ramya , Bowen Kellie K. , Satriotomo Irawan , Liang Jin , Feinstein Douglas L. , Vemuganti Raghu 
Published: January 2007

AbstractThiazolidinediones (TZDs) are synthetic agonists of the ligand‐activated transcription factor peroxisome proliferator‐activated receptor‐γ (PPARγ). TZDs are known to curtail inflammation associated with peripheral organ ischemia. As inflammation precipitates the neuronal death after stroke, we tested the efficacy of TZDs in preventing brain damage following transient middle cerebral artery occlusion (MCAO) in adult rodents. As hypertension and diabetes complicate the stroke outcome, we also evaluated the efficacy of TZDs in hypertensive rats and type‐2 diabetic mice subjected to transient MCAO. Pre‐treatment as well as post‐treatment with TZDs rosiglitazone and pioglitazone significantly decreased the infarct volume and neurological deficits in normotensive, normoglycemic, hypertensive and hyperglycemic rodents. Rosiglitazone neuroprotection was not enhanced by retinoic acid × receptor agonist 9‐cis‐retinoic acid, but was prevented by PPARγ antagonist GW9662. Rosiglitazone significantly decreased the post‐ischemic intercellular adhesion molecule‐1 expression and extravasation of macrophages and neutrophils into brain. Rosiglitazone treatment curtailed the post‐ischemic expression of the pro‐inflammatory genes interleukin‐1β, interleukin‐6, macrophage inflammatory protein‐1α, monocyte chemoattractant protein‐1, cyclooxygenase‐2, inducible nitric oxide synthase, early growth response‐1, CCAAT/enhancer binding protein‐β and nuclear factor‐kappa B, and increased the expression of the anti‐oxidant enzymes catalase and copper/zinc‐superoxide dismutase. Rosiglitazone also increased the expression of the anti‐inflammatory gene suppressor of cytokine signaling‐3 and prevented the phosphorylation of the transcription factor signal transducer and activator of transcription‐3 after focal ischemia. Thus, PPARγ activation with TZDs might be a potent therapeutic option for preventing inflammation and neuronal damage after stroke with promise in diabetic and hypertensive subjects.
Group I metabotropic glutamate receptor‐dependent TRPC channel trafficking in hippocampal neurons
Authors: Wang Min , Bianchi Riccardo , Chuang Shih‐Chieh , Zhao Wangfa , Wong Robert K. S. 
Published: January 2007

AbstractThe group I metabotropic glutamate receptor agonist (S)‐3,5‐dihydroxyphenylglycine (DHPG) elicited two phases of synchronized neuronal (epileptiform) discharges in hippocampal slices: an initial phase of short duration discharges followed by a phase of prolonged discharges. We assessed the involvement of transient receptor potential canonical (TRPC) channels in these responses. Pre‐treatment of hippocampal slices with TRPC channel blockers, 1‐[beta‐[3‐(4‐methoxyphenyl)propoxy]‐4‐methoxyphenethyl]‐1H‐imidazole hydrochloride (SKF96365) or 2‐aminoethoxydiphenyl borate, did not affect the short epileptiform discharges but blocked the prolonged epileptiform discharges. SKF96365 suppressed ongoing DHPG‐induced prolonged epileptiform discharges. Western blot analysis showed that the total TRPC4 or TRPC5 proteins in hippocampal slices were unchanged following DHPG. DHPG increased TRPC4 and TRPC5 in the cytoplasmic compartment and decreased these proteins in the plasma membrane. Translocation of TRPC4 and TRPC5 was suppressed when the epileptiform discharges were blocked by ionotropic glutamate receptor blockers. Translocation of TRPC4 and TRPC5 was also prevented in slices from phospholipase C (PLC) β1 knockout mice, even when synchronized discharges were elicited by the convulsant 4‐aminopyridine. The results suggest that TRPC channels are involved in generating DHPG‐induced prolonged epileptiform discharges. This function of TRPC channels is associated with a neuronal activity‐ and PLCβ1‐dependent translocation of TRPC4 and TRPC5 proteins from the plasmalemma to the cytoplasmic compartment.
Poly(d,l-Lactide-Coglycolide) Particles Containing Gentamicin: Pharmacokinetics and Pharmacodynamics inBrucella melitensis- Infected Mice
Authors: Lecaroz M. C. , Blanco-Prieto M. J. , Campanero M. A. , Salman H. , Gamazo C. 
Published: January 2007

ABSTRACTDrug delivery systems containing gentamicin were studied as a treatment against experimental brucellosis in mice. Micro- and nanoparticles prepared by using poly(d,l-lactide-coglycolide) (PLGA) 502H and microparticles made of PLGA 75:25H were successfully delivered to the liver and the spleen, the target organs forBrucella melitensis. Both polymers have the same molecular weight but have different lactic acid/glycolic acid ratios. Microparticles of PLGA 502H and 75:25H released their contents in a sustained manner, in contrast to PLGA 502H nanoparticles, which were degraded almost completely during the first week postadministration. The values of the pharmacokinetic parameters after administration of a single intravenous dose of 1.5 mg/kg of body weight of loaded gentamicin revealed higher areas under the curve (AUCs) for the liver and the spleen and increased mean retention times (MRTs) compared to those for the free drug, indicating the successful uptake by phagocytic cells in both organs and the controlled release of the antibiotic. Both gentamicin-loaded PLGA 502H and 75:25H microparticles presented similar pharmacokinetic parameter values for the liver, but those made of PLGA 75:25 H were more effective in targeting the antibiotic to the spleen (higher AUCs and MRTs). The administration of three doses of 1.5 mg/kg significantly reduced the load associated with the splenicB. melitensisinfection. Thus, the formulation made with the 75:25H polymer was more effective than that made with 502H microspheres (1.45-log and 0.45-log reductions, respectively, at 3 weeks posttreatment). Therefore, both, pharmacokinetic and pharmacodynamic parameters showed the suitability of 75:25H microspheres to reduce the infection of experimentally infected mice withB. melitensis.
Sequencing and Analysis of the Biosynthetic Gene Cluster of the Lipopeptide Antibiotic Friulimicin in
Actinoplanes friuliensis
Authors: Müller C. , Nolden S. , Gebhardt P. , Heinzelmann E. , Lange C. , Puk O. , Welzel K. , Wohlleben W. , Schwartz D. 
Published: January 2007

ABSTRACT

Actinoplanes friuliensis
produces the lipopeptide antibiotic friulimicin, which is a cyclic peptide with one exocyclic amino acid linked to a branched-chain fatty acid acyl residue. The structural relationship to daptomycin and the excellent antibacterial performance of friulimicin make the antibiotic an attractive drug candidate. The complete friulimicin biosynthetic gene cluster of 24 open reading frames from
A. friuliensis
was sequenced and analyzed. In addition to genes for regulation, self-resistance, and transport, the cluster contains genes encoding peptide synthetases, proteins involved in the synthesis and linkage of the fatty acid component of the antibiotic, and proteins involved in the synthesis of the nonproteinogenic amino acids pipecolinic acid, methylaspartic acid, and 2,3-diaminobutyric acid. By using heterologous gene expression in
Escherichia coli
, we provide biochemical evidence for the stereoselective synthesis of
l
-pipecolinic acid by the deduced protein of the lysine cyclodeaminase gene
pip
. Furthermore, we show the involvement of the
dabA
and
dabB
genes in the biosynthesis of 2,3-diaminobutyric acid by gene inactivation and subsequent feeding experiments.
In Vitro Studies with DQ-113 and Comparison Fluoroquinolones To Determine Propensities To Select Resistance in Gram-Positive Cocci
Authors: Hong Seong Geun , Moland Ellen Smith , Wickman Paul A. , Black Jennifer A. , Hossain Ashfaque , Hanson Nancy D. , Thomson Kenneth S. 
Published: January 2007

ABSTRACT
DQ-113 was compared in vitro to sitafloxacin, moxifloxacin, levofloxacin, and ciprofloxacin for potential to select mutational resistance in multiresistant staphylococci, pneumococci, and enterococci. Its ability to select less-susceptible mutants varied according to species, being lowest with staphylococci, intermediate with pneumococci, and greatest with enterococci.
Heterologous Production of Albicidin: a Promising Approach to Overproducing and Characterizing This Potent Inhibitor of DNA Gyrase
Authors: Vivien Eric , Pitorre Delphine , Cociancich Stéphane , Pieretti Isabelle , Gabriel Dean W. , Rott Philippe C. , Royer Monique 
Published: January 2007

ABSTRACT

The phytotoxin and polyketide antibiotic albicidin produced by
Xanthomonas albilineans
is a highly potent DNA gyrase inhibitor. Low yields of albicidin production have slowed studies of its chemical structure. Heterologous expression of albicidin biosynthetic genes in
X. axonopodis
pv. vesicatoria resulted in a sixfold increase in albicidin production, offering promising strategies for engineering overproduction.
Histidine Decarboxylases and Their Role in Accumulation of Histamine in Tuna and Dried Saury
Authors: Kanki Masashi , Yoda Tomoko , Tsukamoto Teizo , Baba Eiichiroh 
Published: January 2007

ABSTRACT

Histamine-producing bacteria (HPB) such as
Photobacterium phosphoreum
and
Raoultella planticola
possess histidine decarboxylase (HDC), which converts histidine into histamine. Histamine fish poisoning (HFP) is attributable to the ingestion of fish containing high levels of histamine produced by HPB. Because freezing greatly decreases the histamine-producing ability of HPB, especially of
P. phosphoreum
, it has been speculated that HFP is caused by HDC itself from HPB cells autolyzing during frozen storage, even when HPB survive frozen storage. Here we constructed recombinant HDCs of
P. phosphoreum
,
Photobacterium damselae
,
R. planticola
, and
Morganella morganii
and investigated the ability of HDCs to produce sufficient histamine to cause HFP. To elucidate the character of these HDCs, we examined the specific activity of each recombinant HDC at various temperatures, pH levels, and NaCl concentrations. Further, we also investigated the stability of each HDC under different conditions (in reaction buffer, tuna, and dried saury) at various temperatures.
P. damselae
HDC readily produced sufficient histamine to cause HFP in fish samples. We consider that if HDC is implicated as an independent cause of HFP in frozen-thawed fish, the most likely causative agent is HDC of
P. damselae
.
Adaptation of a Luciferase Gene Reporter and
lac
Expression System to
Borrelia burgdorferi
Authors: Blevins Jon S. , Revel Andrew T. , Smith Alexandra H. , Bachlani Gulnaz N. , Norgard Michael V. 
Published: January 2007

ABSTRACT

The development of new genetic systems for studying the complex regulatory events that occur within
Borrelia burgdorferi
is an important goal of contemporary Lyme disease research. Although recent advancements have been made in the genetic manipulation of
B. burgdorferi
, there still remains a paucity of basic molecular systems for assessing differential gene expression in this pathogen. Herein, we describe the adaptation of two powerful genetic tools for use in
B. burgdorferi
. The first is a
Photinus pyralis
firefly luciferase gene reporter that was codon optimized to enhance translation in
B. burgdorferi
. Using this modified reporter, we demonstrated an increase in luciferase expression when
B. burgdorferi
transformed with a shuttle vector encoding the outer surface protein C (OspC) promoter fused to the luciferase reporter was cultivated in the presence of fresh rabbit blood. The second is a
lac
operator/repressor system that was optimized to achieve the tightest degree of regulation. Using the aforementioned luciferase reporter, we assessed the kinetics and maximal level of isopropyl-β-
d
-thiogalactopyranoside (IPTG)-dependent gene expression. This
lac
-inducible expression system also was used to express the gene carried on lp25 required for
b
orrelial
p
ersistence in
t
icks (
bptA
). These advancements should be generally applicable for assessing further the regulation of other genes potentially involved in virulence expression by
B. burgdorferi
.
Screening Marine Fungi for Inhibitors of the C
4
Plant Enzyme Pyruvate Phosphate Dikinase: Unguinol as a Potential Novel Herbicide Candidate
Authors: Motti Cherie A. , Bourne David G. , Burnell James N. , Doyle Jason R. , Haines Dianne S. , Liptrot Catherine H. , Llewellyn Lyndon E. , Ludke Shilo , Muirhead Andrew , Tapiolas Dianne M. 
Published: January 2007

ABSTRACT

A total of 2,245 extracts, derived from 449 marine fungi cultivated in five types of media, were screened against the C
4
plant enzyme pyruvate phosphate dikinase (PPDK), a potential herbicide target. Extracts from several fungal isolates selectively inhibited PPDK. Bioassay-guided fractionation of one isolate led to the isolation of the known compound unguinol, which inhibited PPDK with a 50% inhibitory concentration of 42.3 ± 0.8 μM. Further kinetic analysis revealed that unguinol was a mixed noncompetitive inhibitor of PPDK with respect to the substrates pyruvate and ATP and an uncompetitive inhibitor of PPDK with respect to phosphate. Unguinol had deleterious effects on a model C
4
plant but no effect on a model C
3
plant. These results indicate that unguinol inhibits PPDK via a novel mechanism of action which also translates to an herbicidal effect on whole plants.
De Novo Sphingolipid Synthesis Is Essential for Viability, but Not for Transport of Glycosylphosphatidylinositol-Anchored Proteins, in African Trypanosomes
Authors: Sutterwala Shaheen S. , Creswell Caleb H. , Sanyal Sumana , Menon Anant K. , Bangs James D. 
Published: January 2007

ABSTRACT

De novo sphingolipid synthesis is required for the exit of glycosylphosphatidylinositol (GPI)-anchored membrane proteins from the endoplasmic reticulum in yeast. Using a pharmacological approach, we test the generality of this phenomenon by analyzing the transport of GPI-anchored cargo in widely divergent eukaryotic systems represented by African trypanosomes and HeLa cells. Myriocin, which blocks the first step of sphingolipid synthesis (serine + palmitate → 3-ketodihydrosphingosine), inhibited the growth of cultured bloodstream parasites, and growth was rescued with exogenous 3-ketodihydrosphingosine. Myriocin also blocked metabolic incorporation of [
3
H]serine into base-resistant sphingolipids. Biochemical analyses indicate that the radiolabeled lipids are not sphingomyelin or inositol phosphorylceramide, suggesting that bloodstream trypanosomes synthesize novel sphingolipids. Inhibition of de novo sphingolipid synthesis with myriocin had no adverse effect on either general secretory trafficking or GPI-dependent trafficking in trypanosomes, and similar results were obtained with HeLa cells. A mild effect on endocytosis was seen for bloodstream trypanosomes after prolonged incubation with myriocin. These results indicate that de novo synthesis of sphingolipids is not a general requirement for secretory trafficking in eukaryotic cells. However, in contrast to the closely related kinetoplastid
Leishmania major
, de novo sphingolipid synthesis is essential for the viability of bloodstream-stage African trypanosomes.
Molecular Cloning of Apicoplast-Targeted
Plasmodium falciparum
DNA Gyrase Genes: Unique Intrinsic ATPase Activity and ATP-Independent Dimerization of PfGyrB Subunit
Authors: Dar Mohd Ashraf , Sharma Atul , Mondal Neelima , Dhar Suman Kumar 
Published: January 2007

ABSTRACT

DNA gyrase, a typical type II topoisomerase that can introduce negative supercoils in DNA, is essential for replication and transcription in prokaryotes. The apicomplexan parasite
Plasmodium falciparum
contains the genes for both gyrase A and gyrase B in its genome. Due to the large sizes of both proteins and the unusual codon usage of the highly AT-rich
P. falciparum gyrA
(Pf
gyrA
) and Pf
gyrB
genes, it has so far been impossible to characterize these proteins, which could be excellent drug targets. Here, we report the cloning, expression, and functional characterization of full-length PfGyrB and functional domains of PfGyrA. Unlike
Escherichia coli
GyrB, PfGyrB shows strong intrinsic ATPase activity and follows a linear pattern of ATP hydrolysis characteristic of dimer formation in the absence of ATP analogues. These unique features have not been reported for any known gyrase so far. The Pf
gyrB
gene complemented the
E. coli
gyrase temperature-sensitive strain, and, together with the N-terminal domain of PfGyrA, it showed typical DNA cleavage activity. Furthermore, PfGyrA contains a unique leucine heptad repeat that might be responsible for dimerization. These results confirm the presence of DNA gyrase in eukaryotes and confer great potential for drug development and organelle DNA replication in the deadliest human malarial parasite,
P. falciparum
.