bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uncoupling is without an effect on the production of reactive oxygen species by in situ synaptic mitochondria
Authors: Tretter Laszlo , Adam‐Vizi Vera 
Published: September 2007

AbstractEarlier reports that generation of reactive oxygen species (ROS) by isolated mitochondria supported by succinate was sensitive to small changes in the mitochondrial membrane potential (ΔΨm) served as a basis for the concept of ‘mild uncoupling’ suggesting that a few millivolts decrease in ΔΨm would be beneficial in neuroprotection because of reducing the production of ROS by mitochondria. In this study, we tested whether ROS generation by in situ mitochondria, which function in a normal cytosolic environment and oxidize glucose‐derived physiological substrates, is also dependent on changes in ΔΨm. The release of H2O2 was measured by the Amplex red fluorescence assay in freshly prepared isolated nerve terminals, synaptosomes incubated in a glucose‐containing medium. ΔΨm was decreased by the uncoupler carbonyl cyanide‐p‐trifluoromethoxyphenyl‐hydrazon (FCCP) (10–200 nmol/L), which accelerated the oxygen consumption, decreased the NADH level and induced depolarization, as shown by the fluorescence indicator JC‐1, in in situ mitochondria. These changes were detected at already the smallest FCCP concentration. H2O2 generation, however, was found to be unaltered by FCCP at any of the applied concentration. Depolarization of mitochondria was also induced by veratridine (40 μmol/L), which enhances the cytosolic Na+ concentration and imposes an ATP demand in synaptosomes. The accelerated oxygen consumption and the small depolarization of in situ mitochondria by veratridine were not paralleled by any significant alteration in the ROS generation. These findings indicate that a basal ROS generation by in situ mitochondria is not sensitive to changes in ΔΨm challenging the rational of the ‘mild uncoupling’ theory for neuroprotection and suggest that the ΔΨm‐dependent characteristics of ROS generation is limited mainly to well‐coupled succinate‐supported isolated mitochondria.
Retinoid receptors in chronic degeneration of the spinal cord: observations in a rat model of amyotrophic lateral sclerosis
Authors: Jokic Natasa , Ling Yong Yong , Ward Rachael E. , Michael‐Titus Adina T. , Priestley John V. , Malaspina Andrea 
Published: September 2007

AbstractChanges in distribution and expression of retinoid receptors may be part of a spinal cord protective response to acute injury and to chronic degeneration. In this study, we have combined RNA and protein expression analysis to characterize the expression profile of retinoid receptors in the lumbar spinal cord of the superoxide dismutase 1 G93A mutant rat model of amyotrophic lateral sclerosis, a fatal neurodegenerative disorder causing extensive motor neuron loss. We also report a nonsignificant change in RNA expression of binding proteins and metabolizing enzymes for retinol and retinoic acid in the mutant rat spinal cord at end‐stage disease. Only retinoid X receptor beta (RXRbeta), and to a lesser extent retinoic acid receptor beta and alpha (RARbeta/alpha) were reliably detected in lumbar spinal cord at an early pre‐symptomatic phase and throughout the disease progression. The expression of RXRbeta in lamina II neurons in the dorsal horn of transgenic and wild type (WT) animals was associated with extensive astrocyte staining in end‐stage lumbar spinal cord from transgenic rats. RARbeta and RARalpha diffuse staining of large motor neurons in the pre‐symptomatic transgenic and in the WT lumbar cord appear to decline in end‐stage disease, when a selective and strong gamma motor neuron RARalpha staining becomes evident. As gliosis and motor neuron loss are key pathogenic features in amyotrophic lateral sclerosis, the selective expression of retinoid receptors in astrocytes and motor neurons may provide further clues to the role of retinoid signalling in neurodegeneration and suggest new treatment strategies based on retinoid‐modulating agents.
Pituitary adenylate cyclase‐activating polypeptide is up‐regulated in cortical pyramidal cells after focal ischemia and protects neurons from mild hypoxic/ischemic damage
Authors: Stumm Ralf , Kolodziej Angela , Prinz Vincent , Endres Matthias , Wu Dai‐Fei , Höllt Volker 
Published: September 2007

AbstractThe protective effect of pituitary adenylate cyclase‐activating polypeptide (PACAP) in stroke models is poorly understood. We studied patterns of PACAP, vasoactive intestinal peptide, and the PACAP‐selective receptor PAC1 after middle cerebral artery occlusion and neuroprotection by PACAP in cortical cultures exposed to oxygen/glucose deprivation (OGD). Within hours, focal ischemia caused a massive, NMDA receptor (NMDAR)‐dependent up‐regulation of PACAP in cortical pyramidal cells. PACAP expression dropped below the control level after 2 days and was normalized after 4 days. Vasoactive intestinal peptide expression was regulated oppositely to that of PACAP. PAC1 mRNA showed ubiquitous expression in neurons and astrocytes with minor changes after ischemia. In cultured cortical neurons PACAP27 strongly activated Erk1/2 at low and p38 MAP kinase at higher nanomolar concentrations via PAC1. In astrocyte cultures, effects of PACAP27 on Erk1/2 and p38 were weak. During OGD, neurons showed severely reduced Erk1/2 activity and dephosphorylation of Erk1/2‐regulated Ser112 of pro‐apoptotic Bad. PACAP27 stimulation counteracted Erk1/2 inactivation and Bad dephosphorylation during short‐term OGD but was ineffective after expanded OGD. Consistently, PACAP27 caused MEK‐dependent neuroprotection during mild but not severe hypoxic/ischemic stress. While PACAP27 protected neurons at 1–5 nmol/L, full PAC1 activation by 100 nmol/L PACAP exaggerated hypoxic/ischemic damage. PACAP27 stimulation of astrocytes increased the production of Akt‐activating factors and conferred ischemic tolerance to neurons. Thus, ischemia‐induced PACAP may act via neuronal and astroglial PAC1. PACAP confers protection to ischemic neurons by maintaining Erk1/2 signaling via neuronal PAC1 and by increasing neuroprotective factor production via astroglial PAC1.
G protein‐coupled receptor oligomerization provides the framework for signal discrimination1
Authors: Maggio Roberto , Innamorati Giulio , Parenti Marco 
Published: September 2007

AbstractThe idea that G protein‐coupled receptors (GPCRs) may undergo homo‐ or hetero‐oligomerization, although highly controversial up to a few years ago, has recently gained wide acceptance. The recognition that GPCRs may exhibit either dimeric or oligomeric structures is based upon a large body of biochemical and biophysical evidence. While much effort has been spent to demonstrate the mechanism(s) by which GPCRs interact with each other, the physiological relevance of this phenomenon remains rather elusive. GPCR oligomerization has been proposed to play a role in receptor ontogeny by either chaperoning protein folding or controlling trafficking to the cell surface. However, the acquisition of these roles does not rule out the possibility that oligomeric receptors may have additional functions, once they are brought to the cell surface. Herein, we propose that protein–protein as well as protein–lipid interactions may provide the structural basis for organizing distinct cell compartments along the plasma membrane where different extracellular signals may be perceived and discriminated.
Circadian phosphorylation of ATF‐2, a potential activator of Period2 gene transcription in the chick pineal gland
Authors: Shimizu Fumiko , Fukada Yoshitaka 
Published: September 2007

AbstractStimulus‐induced transcription of the Period gene is a critical step for phase‐shift of vertebrate circadian systems. The promoter region of chicken Period2 contains a canonical calcium/cAMP‐responsive element, but its functional relevance is not known. The present study shows that cAMP‐responsive element‐binding protein (CREB) and activating transcription factor‐2 (ATF‐2) bind to the promoter region of the Period2 gene in the chick pineal gland. In transient transfection assays, a reporter construct containing 0.7‐kbp upstream region of chicken Period2 was transactivated by ATF‐2, but it was poorly responsive to CREB. In the chick pineal gland, phosphorylation of CREB protein at the kinase‐inducible domain was negatively regulated by light. On the other hand, phosphorylation of ATF‐2 at the amino‐terminal transactivation domain exhibited a circadian rhythm with a daytime peak, suggesting a role for ATF‐2 in circadian rhythmicity in the chick pineal gland.
Inhibition of cortical astrocyte differentiation by Hes6 requires amino‐ and carboxy‐terminal motifs important for dimerization and phosphorylation
Authors: Belanger‐Jasmin Stephanie , Llamosas Estelle , Tang Yeman , Joachim Kerline , Osiceanu Ana‐Maria , Jhas Sumit , Stifani Stefano 
Published: September 2007

AbstractHairy/Enhancer of split (Hes) 6 is a basic helix‐loop‐helix protein that interacts with the transcriptional co‐repressor, Groucho, and antagonizes the neural functions of the Notch pathway. More specifically, mouse Hes6 regulates cerebral corticogenesis by promoting neurogenesis and suppressing astrocyte differentiation. The molecular mechanisms underlying the anti‐astrogenic function of Hes6 are poorly defined. Here we describe studies aimed at testing whether Hes6 inhibits astrocyte differentiation by antagonizing the transcription repression activity of Notch‐activated Hes family members like Hes1. It is reported that Hes6 preferentially forms homodimers. Heterodimerization with Hes1 is antagonized in part by a conserved N‐terminal patch of negatively charged residues. Mutation of this motif enhances heterodimerization with Hes1 and increases Hes6 ability to antagonize Hes1‐mediated transcriptional repression. However, this mutation does not increase, but instead decreases, the anti‐astrogenic activity of Hes6. It is shown further that Hes6 harbors a second conserved sequence, a C‐terminal SPXXSP motif. This sequence is phosphorylated by the mitogen activated protein kinase pathway and its mutation disrupts the anti‐astrogenic activity of Hes6 without affecting its ability to suppress Hes1. Together, these observations suggest that Hes6 homodimers regulate astrocyte differentiation through mechanisms that depend on the phosphorylation of Hes6 C‐terminal domain but are independent of its ability to suppress Hes1‐mediated transcriptional repression.
Cell‐type specific induction of tryptophan hydroxylase‐2 transcription by calcium mobilization
Authors: Lenicov Federico Remes , Lemonde Sylvie , Czesak Margaret , Mosher Tera M. , Albert Paul R. 
Published: September 2007

AbstractAlterations in brain serotonin levels are implicated in major depression and are regulated by tryptophan hydroxylase‐2 (TPH2). To study its regulation, we measured TPH2 RNA by quantitative RT‐PCR in differentiated serotonergic rat raphe RN46A and GH4C1 pituitary cells, which express TPH2. Upon calcium mobilization using KCl (40 mmol/L), TPH2 RNA was rapidly (1 h) and strongly (> 10‐fold) induced in differentiated RN46A cells, but not in GH4C1 cells. This effect was blocked by actinomycin D, implicating transcriptional activation. Similarly, calcium ionophore ionomycin induced TPH2 RNA by threefold in RN46A cells. To address the promoter sites involved, the transcription start site was identified and a series of TATA‐containing TPH2 promoter‐luciferase constructs were analyzed. In differentiated RN46A cells, the TPH2 promoter was induced 2.5‐fold by ionomycin, similar to its action on TPH2 RNA. By contrast, ionomycin had no effect on TPH2 promoter activity in GH4C1 cells or TPH2‐negative L6 myoblasts. Ionomycin sensitivity was localized to within 88 bp of the start site, containing putative CCATT‐enhancer binding protein element, activator protein‐1 and ‐2 (AP‐1, AP‐2) elements. These results are the first to identify calcium‐mediated regulation of the proximal TPH2 promoter as critical for cell‐specific TPH2 expression.
Chronic exposure to sub‐lethal beta‐amyloid (Aβ) inhibits the import of nuclear‐encoded proteins to mitochondria in differentiated PC12 cells*
Authors: Sirk Daniel , Zhu Ziping , Wadia Jehangir S. , Shulyakova Natalya , Phan Nam , Fong Jamie , Mills Linda R. 
Published: September 2007

AbstractStudies on amyloid beta (Aβ|), the peptide thought to play a crucial role in the pathogenesis of Alzheimer’s disease, have implicated mitochondria in Aβ‐mediated neurotoxicity. We used differentiated PC12 cells stably transfected with an inducible green fluorescent protein (GFP) fusion protein containing an N′‐terminal mitochondrial targeting sequence (mtGFP), to examine the effects of sub‐lethal Aβ on the import of nuclear‐encoded proteins to mitochondria. Exposure to sub‐lethal Aβ25–35 (10 μmol/L) for 48 h inhibited mtGFP import to mitochondria; average rates decreased by 20 ± 4%. Concomitant with the decline in mtGFP, cytoplasmic mtGFP increased significantly while mtGFP expression and intramitochondrial mtGFP turnover were unchanged. Sub‐lethal Aβ1–42 inhibited mtGFP import and increased cytoplasmic mtGFP but only after 96 h. The import of two endogenous nuclear‐encoded mitochondrial proteins, mortalin/mtHsp70 and Tom20 also declined. Prior to the decline in import, mitochondrial membrane potential (mmp), and reactive oxygen species levels were unchanged in Aβ‐treated cells versus reverse phase controls. Sustained periods of decreased import were associated with decreased mmp, increased reactive oxygen species, increased vulnerability to oxygen‐glucose deprivation and altered mitochondrial morphology. These findings suggest that an Aβ‐mediated inhibition of mitochondrial protein import, and the consequent mitochondrial impairment, may contribute to Alzheimer’s disease.
Timing of potential and metabolic brain energy
Authors: Korf Jakob , Gramsbergen Jan Bert 
Published: September 2007

AbstractThe temporal relationship between cerebral electro‐physiological activities, higher brain functions and brain energy metabolism is reviewed. The duration of action potentials and transmission through glutamate and GABA are most often less than 5 ms. Subjects may perform complex psycho‐physiological tasks within 50 to 200 ms, and perception of conscious experience requires 0.5 to 2 s. Activation of cerebral oxygen consumption starts after at least 100 ms and increases of local blood flow become maximal after about 1 s. Current imaging technologies are unable to detect rapid physiological brain functions. We introduce the concepts of potential and metabolic brain energy to distinguish trans‐membrane gradients of ions or neurotransmitters and the capacity to generate energy from intra‐ or extra‐cerebral substrates, respectively. Higher brain functions, such as memory retrieval, speaking, consciousness and self‐consciousness are so fast that their execution depends primarily on fast neurotransmission (in the millisecond range) and action‐potentials. In other words: brain functioning requires primarily maximal potential energy. Metabolic brain energy is necessary to restore and maintain the potential energy.
Increased expression of lysosomal acid phosphatase in CLN3‐defective cells and mouse brain tissue
Authors: Pohl Sandra , Mitchison Hannah M. , Kohlschütter Alfried , Diggelen Otto van , Braulke Thomas , Storch Stephan 
Published: September 2007

AbstractJuvenile neuronal ceroid lipofuscinosis (Batten disease) is a neurodegenerative disorder caused by defective function of the lysosomal membrane glycoprotein CLN3. The activity of the lysosomal acid phosphatase (LAP/ACP2) was found to be significantly increased in the cerebellum and brain stem of Cln3‐targeted mice during the early stages of postnatal life. Histochemical localization studies revealed an increased LAP/ACP2 staining intensity in neurons of the cerebral cortex of 48‐week‐old Cln3‐targeted mice as compared with controls. Additionally, the expression of another lysosomal membrane protein LAMP‐2 was increased in all brain areas. Knockdown of CLN3 expression in HeLa cells by RNA interference also resulted in increased LAP/ACP2 and LAMP‐2 expression. Finally in fibroblasts of two juvenile neuronal ceroid lipofuscinosis patients elevated levels of LAP/ACP2 were found. Both activation of gene transcription and increased protein half‐life appear to contribute to increased LAP/ACP2 protein expression in CLN3‐deficient cells. The data suggest that lysosomal dysfunction and accumulation of storage material require increased biogenesis of LAP/ACP2 and LAMP‐2 positive membranes which makes LAP/ACP2 suitable as biomarker of Batten disease.
PERMANENT GENETIC RESOURCES: Identification of nuclear microsatellite loci for Ipomopsis aggregata and the distribution of pairwise relatedness in a natural population
Authors: STEARNS FRANK , BOLES SANDRA , HURSTON HEATHER , VO TANYA , BUTLER DALE , SHUHAM WALTER , JUENGER THOMAS E. 
Published: September 2007

AbstractNine microsatellite loci were developed from enriched libraries of scarlet gilia (Ipomopsis aggregata). A screen of 160 individuals from a population identified reduced levels of heterozygosity, low levels of relatedness, and weak spatial genetic patterns. The population inbreeding coefficient was calculated to be 0.19 (SE = 0.04). These patterns are consistent with those expected from low levels of biparental inbreeding in an obligate outcrosser and extensive seed and pollen dispersal. These preliminary data confirm the usefulness of microsatellite markers for breeding system studies of I. aggregata.
Gastric Stasis Occurs in Spontaneous, Visually Induced, and Interictal Migraine
Authors: Aurora Sheena , Kori Shashidhar , Barrodale Patricia , Nelsen Andrew , McDonald Susan 
Published: September 2007

Objective.— To evaluate and compare gastric motility and emptying during spontaneous migraine to previous observations from induced migraine.Blackground.— We have previously demonstrated a delay in gastric emptying both during the interictal period and during an induced migraine. A limitation noted in these studies was whether there are differences gastrointestinally during a visually induced migraine compared to spontaneous migraines. To address this, 9 additional studies have been performed to ascertain if there is a similar delay during spontaneous migraineMethods.— Gastric scintigraphy using a standard meal was performed in 3 subjects during 3 periods: spontaneous migraine, induced migraine, and interictal period.Results.— On average, the time to half emptying was delayed during spontaneous migraine (124 minutes), during induced migraine (182 minutes), and during the interictal period migraine (243 minutes) compared to normative values established at our center (112 minutes). On average, similar gastric slowing was seen in all 3 groups when the percentage of nuclear material remaining in the stomach at 2 hours was measured.Conclusions.— This study provides additional evidence of gastric stasis in migraineurs interictally during induced and spontaneous migraine.
Lingual Retention and the Elimination of the Visible Clasp Arm
Authors: BRUDVIK JAMES S. , PALACIOS ROSARIO 
Published: September 2007

ABSTRACTThe modern removable partial denture (RPD), in response to the increased esthetic demands of our patients, is no longer acceptable if it requires visible buccal and facial clasp arms for retention. By eliminating the bracing arm and having its functions taken by paralleled guide planes and precise, positive rests, the retentive element, a lingual circumferential wire clasp arm, will provide the same amount of retentive force as if it were placed on the buccal surface and will not be visible. Designs for the major connector either plate the lingual surface of the abutment or, as in a lingual bar, leave that surface open. Both of these situations are adaptable to the lingual retentive clasp and are illustrated in this article.CLINICAL SIGNIFICANCEDesign features such as metal clasps needed for the retention of RPDs can be very unsightly, creating an esthetic problem. This article reviews the concepts for creating lingual clasp arms that enhance the esthetic quality of prostheses.(J Esthet Restor Dent 19:247–255, 2007)
Prolonged imatinib‐induced myelosuppression in chronic myeloid leukaemia with an unusually long survival
Authors: Busuttil D. P. 
Published: September 2007

SummaryA case of Philadelphia chromosome positive chronic myeloid leukaemia (CML) with the longest survival ever reported in the medical literature is presented. The duration of the chronic phase was 29 years, the overall survival being 31 years. The clinical course, when challenged with imatinib in the later stages of the disease, was at variance with what is to be expected from the experience in similar situations. Lifelong myelosuppression resulted that interfered with further therapy and contributed to the demise of the patient from sepsis three years later. Caution is suggested with the use of imatinib in fibrotic CML with a low platelet count.
A Model of early to middle Miocene Deep Ocean circulation for the Atlantic and Indian Oceans
Authors: Ramsay Anthony T. S. , Smart Christopher W. , Zachos James C. 
Published: September 2007

Abstract

Tethyan Outflow Water (TOW), characterized by high benthic δ
13
C values, was a component of the early Miocene deep water mass of the Atlantic (
c.
20 and
c.
13 Ma) and Indian (
c.
20 and
c.
14.5 Ma) Oceans. Fluctuations in temperature, salinity and quantity of dissolved oxygen coincided with high abundances of infaunal, smooth-walled bolivinids within the Atlantic and Indian Ocean TOW between 19.5 and 16.5 Ma.

High δO values recorded in the Atlantic water mass may have originated, in part, from evaporation and the formation of warm, saline water within the Tethys. The southward flowing Atlantic TOW at depths of 2–4.5 km enhanced meridional heat transport. It was overlain by Northern Component Water (NCW) with a lower δC signal. TOW and NCW were replaced by southward flowing North Atlantic Deep Water at
c.
13 Ma when cold dense Norwegian—Greenland Sea water flowed across the Greenland—Scotland Ridge.

Indian Ocean TOW was restricted laterally by the Chagos—Lacadive Ridge, and vertically (1.3 to 3 km) by overlying intermediate water, characterized by the occurrence of coarse-walled bolivinids, and underlying deep water characterized by high abundances (>10%) of
Nuttallides umboniferus
. The coarse-walled bolivinid and ‘
N. umboniferus
’ faunas were associated with lower temperature, salinity and higher oxygen concentrations. Tethyan outflow to the northwest Indian Ocean ended at
c.
14.5 Ma, probably in response to the closure of a gateway, and resulted in a two-component deep water mass structure. The coeval increase in the relative abundances of
N. umboniferus
at Indian Ocean Sites 237 (
c.
2 km) and 710 (
c.
3.5 km), at
c.
13 Ma, probably records the impact of this change on the nature of Indian Ocean deep water at depths between 2 and 4 km.

The termination of the Atlantic and, to a lesser extent, Indian Ocean TOW contributed to global cooling and to the expansion of the Antarctic Ice Sheet by limiting the meridional heat transport.