bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondrial biology in Alzheimer’s disease pathogenesis
Authors: Galindo María F. , Ikuta Ichiro , Zhu Xiongwei , Casadesus Gemma , Jordán Joaquín 
Published: May 2010

J. Neurochem.(2010)114, 933–945.AbstractDespite the increasing knowledge of Alzheimer’s disease (AD) management with novel pharmacologic agents, most of them are only transiently fixing symptomatic pathology. Currently there is rapid growth in the field of neuroprotective pharmacology and increasing focus on the involvement of mitochondria in this devastating disease. This review is directed at understanding the role of mitochondria‐mediated pathways in AD and integrating basic biology of the mitochondria with knowledge of possible pharmacologic targets for AD treatment in an attempt to elucidate novel mitochondria‐driven therapeutic interventions useful to both clinical and basic research.
Antagonist‐D2S‐dopamine receptors interactions in intact Chinese recombinant ovary cells
Authors: Packeu Ann , Béghin Tim , De Backer Jean‐Paul , Vauquelin Georges 
Published: May 2010

AbstractD2‐type dopamine receptors are major recognition sites for antipsychotic drugs. There are two splice variants: D2Sand D2Lwith an additional 29 amino acid sequence in the third intracellular loop. Only little comparative information is hitherto available about their pharmacological properties and none of these studies dealt with intact cell systems. This prompted us to investigate the binding properties of [3H]‐raclopride, a hydrophilic benzamide, and [3H]‐spiperone, a highly hydrophobic butyrophenone, to intact CHO cells expressing recombinant human D2L‐receptors. Presently, we have repeated and extended this experimental approach to the human D2S‐receptors in the same cell system. Except for a slower dissociation of [3H]‐spiperone from D2S, the binding properties of these and other antagonists were not significantly different for both isoforms (P > 0.05). The very slow dissociation of the atypical antipsychotic clozapine was surprising in light of its low affinity. Two experiments pointed out the existence of non‐competitive interactions between raclopride and spiperone for D2Sas well as D2L(A. Packeu, J. P. De Backer & G. Vauquelin, in preparation). Alongside the different physicochemical properties of these ligands, this finding fits with a model wherein the hydrophilic raclopride approaches the D2L‐receptor from the aqueous phase, while the hydrophobic spiperone approaches the receptor by lateral diffusion between the membrane lipids. These different modes of approach could imply the existence of topologically distinct ligand binding sites at D2‐receptors.
Report of the Editor‐in‐Chief
Authors: Harvey David 
Published: May 2010

Abstract2009 has seen a further increase in submissions to the Journal, which continue to show an increasingly international pattern, although with no corresponding increase in accepted papers. Response times continue to meet our target of four months, with fewer regrettable lapses, and an improvement in mean time to decision from 2008. The JAE’s citation impact factor has improved to 1.2 in 2008. Wiley‐Blackwell continue to provide a strong publishing platform with the full archive of JAE papers now online.
Exsolution of dolomite and application of calcite–dolomite solvus geothermometry in high‐grade marbles: an example from Skallevikshalsen, East Antarctica
Authors: MIZUOCHI H. , SATISH‐KUMAR M. , MOTOYOSHI Y. , MICHIBAYASHI K. 
Published: May 2010

AbstractCalcite–dolomite solvus geothermometry is a versatile method for the estimation of metamorphic temperature because of its simplicity. However, in medium‐ to high‐grade metamorphic rocks the accuracy of estimating temperature by the integration of unmixed dolomite and calcite is hampered by the heterogeneous distribution of unmixed dolomite, difficulties in distinguishing between preexisting and exsolved dolomite and demarcating grain boundaries. In this study, it is shown that calcite–dolomite solvus thermometry can be applied to calcite inclusions in forsterite and spinel for the estimation of peak metamorphic temperature in granulite facies marbles from Skallevikshalsen, East Antarctica. The marbles are comprised of a granoblastic mineral assemblage of calcite + dolomite + forsterite + diopside + spinel + phlogopite ± apatite, characteristic of granulite facies metamorphic conditions. Forsterite, spinel and apatite frequently contain ‘negative crystal’ inclusions of carbonates that display homogeneously distributed dolomite lamellae. On the basis of narrow ranges of temperature (850–870 °C) recorded from carbonate inclusions compared with the range from matrix carbonate it is regarded that the inclusion carbonates represent a closed system. Furthermore, this estimate is consistent with dolomite–graphite carbon isotope geothermometry, and is considered to be the best estimate of peak metamorphic temperature for this region. Matrix calcite records different stages of retrograde metamorphism and re‐equilibration of calcite that continued until Mg diffusion ceased at ∼460 °C. Electron backscattered diffraction (EBSD) results together with morphological features of unmixed coarse tabular dolomite suggest anisotropic diffusion and mineral growth are influenced by crystallographic orientation. Identification of sub‐grain boundaries and formation of fine‐grained unmixing in calcite rims suggest the presence of grain boundary fluids in the late retrograde stages of metamorphic evolution. These results, thus, demonstrate the usefulness of carbonate inclusion geothermometry in estimating the peak metamorphic temperatures of high‐grade terranes and the application of EBSD in understanding the unmixing behaviour of minerals with solid solutions.
Mössbauer spectroscopy studies of the valence state of iron in chromite from the Luobusa massif of Tibet: implications for a highly reduced deep mantle
Authors: RUSKOV T. , SPIROV I. , GEORGIEVA M. , YAMAMOTO S. , GREEN H. W. , McCAMMON C. A. , DOBRZHINETSKAYA L. F. 
Published: May 2010

AbstractMössbauer spectroscopy was applied to study the valence state of iron in chromite from massive, nodular and disseminated podiform chromitite ores of the Luobasa ophiolite massif of Tibet. The results show that Fe3+/ΣFe = 0.42 in chromite from massive ore, and Fe3+/ΣFe = 0.22 in chromite from nodular and disseminated ores. The massive ore records traces of ultra high pressure mineralogical assemblages, such as diamond inclusions in OsIr alloys, exsolution lamellae of coesite and diopside in chromite, inclusions of metal‐nitrides, native iron and others, which suggests a strongly reducing environment. In contrast, chromite from nodular and disseminated ore contains abundant low‐pressure OH‐bearing mineral inclusions whose formation requires a more oxidizing environment. The high value of Fe3+/ΣFe in the ‘reduced’ massive ore is explained by crystallographic stabilization of Fe3+ in a high‐pressure polymorph of chromite deep in the upper mantle despite low ambient fO2 conditions. The presence of high‐pressure phases within the massive chromitite ore requires that the latter, together with its host peridotite, was transported in the solid state from a highly reduced deep mantle environment to shallow depths beneath an ocean spreading centre. It is suggested that in the low‐pressure environment of the spreading centre, the deep‐seated, reduced, massive chromitites partially reacted with their host peridotite in the presence of hydrous melt, yielding the nodular and disseminated chromitite ores. The preponderance of evidence suggests that the latter interaction involved boninitic melts in a supra‐subduction zone environment as proposed previously.
Retrograde melt–residue interaction and the formation of near‐anhydrous leucosomes in migmatites
Authors: WHITE R. W. , POWELL R. 
Published: May 2010

AbstractConsidering physical segregation of melt from its residue, the chemical potentials of the components (oxides) are the same in both when segregation occurs. Then, as P–T conditions change, gradients in chemical potential are established between the melt‐rich domains and residue permitting diffusional interaction to occur. In particular, on cooling, the chemical potential of H2O becomes higher in the melt segregation than in the residue, particularly when biotite becomes stable in the residue assemblage. Diffusion of water from the melt to the residue promotes crystallization of anhydrous products from the melt and hydrous products in the residue. This diffusive process, when coupled with melt loss from the rocks subsequent to some degree of crystallization, can result in a significant degree of anhydrous leucosome being preserved in a migmatite with only minor retrogression of the residue. If H2O can diffuse between the melt segregation and all of the residue, then no apparent selvedge between the two will be observed. Alternatively, if H2O can diffuse between the melt segregation and only part of the residue, then a distinct selvedge may be produced. Diffusion of H2O into the residue may be in part responsible for the commonly anhydrous nature of leucosomes, especially in granulite facies migmatites. Diffusion of other relatively mobile species such as Na2O and K2O has a lesser effect on overall melt crystallization but can change the proportion of quartz, plagioclase and K‐feldspar in the resultant leucosome. The diffusion of H2O out of the melt results in the enhanced crystallization of the melt in the segregation and increases the amount of resulting anhydrous leucosome relative to the amount produced if melt crystallized in chemical isolation from the residue. For high residue:melt ratios, the proportion of resulting near‐anhydrous leucosome can approach that of the proportion of melt present at the onset of cooling with only minor loss of melt from a given segregation required. Crystallization of melt segregations via the diffusion of H2O out of them into the host may also play a major role in driving melt‐rich segregations across key rheological transitions that would allow the expulsion of remaining melt from the system.
When clinical trials make history: Demonstrating efficacy of new antiepileptic drugs as monotherapy
Authors: Perucca Emilio 
Published: May 2010

SummaryRegulatory requirements to demonstrate the efficacy of novel antiepileptic drugs (AEDs) as monotherapy differ between Europe and the United States. European regulators require a comparison with an established, optimally dosed AED, typically using a noninferiority design, whereas the U.S. Food and Drug Administration (FDA) demands demonstration of superiority versus a comparator. Because placebo cannot be used as sole therapy and it is unrealistic to expect that a new AED will be more efficacious than established agents at full dosages, superiority monotherapy trials in epilepsy have traditionally relied on inclusion of controls treated with a suboptimal (low‐dose) comparator. In the most common design, refractory patients are randomized to conversion to monotherapy with a full dose of the investigational agent or a low‐dose active control, and are required to exit the trial if seizures deteriorate. Efficacy is demonstrated when exit rates are lower in the full‐dose group than in controls. Although this design is efficient in demonstrating superiority, the use of suboptimal treatments has been increasingly criticized on ethical grounds. A meta‐analysis has now demonstrated that patients randomized to suboptimal treatments in all previous trials had similar outcomes, thereby allowing the build up of a dataset of historical controls against which response to investigational AEDs can be compared in future trials. Use of historical controls has been accepted by the FDA, subject to compliance with rigorous methodologic requirements. Although the avoidance of suboptimal treatments in future trials is a welcome development, the conversion‐to‐monotherapy design is still far from being fully satisfactory and is not exempt from methodologic concerns.
Acute encephalopathy with a truncation mutation in the SCN1A gene: A case report
Authors: Takayanagi Masaru , Haginoya Kazuhiro , Umehara Naoki , Kitamura Taro , Numata Yurika , Wakusawa Keisuke , Hino‐Fukuyo Naomi , Mazaki Emi , Yamakawa Kazuhiro , Ohura Toshihiro , Ohtake Masatoshi 
Published: May 2010

SummaryA girl aged 1 year 9 months had recurrent episodes of febrile status epilepticus. She recovered completely after the first three episodes. However, at 9 months she developed acute encephalopathy resulting in severe neurologic sequelae. Diffusion‐weighted magnetic resonance imaging revealed diffuse high‐intensity signals over the cortex and subcortical white matter in the acute phase and severe diffuse cerebral atrophy in the chronic phase. Mutations were detected in the neuronal voltage‐gated sodium channel alpha subunit type 1 (SCN1A) gene. SCN1A sequence analysis revealed a truncation mutation: ex1‐c.126Adel (D43fs). Our patient was likely afflicted by severe myoclonic epilepsy in infancy, and the fourth episode of status epilepticus was similar to acute encephalopathy. This report provides further insight into the molecular pathophysiology underlying acute encephalopathy.
Strain Differences in Behavioral Inhibition in a Go/No‐go Task Demonstrated Using 15 Inbred Mouse Strains
Authors: Gubner Noah R. , Wilhelm Clare J. , Phillips Tamara J. , Mitchell Suzanne H. 
Published: May 2010

Background: High levels of impulsivity have been associated with a number of substance abuse disorders including alcohol abuse. Research has not yet revealed whether these high levels predate the development of alcohol abuse.Methods: The current study examined impulsivity in 15 inbred strains of mice (A/HeJ, AKR/J, BALB/cJ, C3H/HeJ, C57BL/6J, C57L/J, C58/J, CBA/J, DBA/1J, DBA/2J, NZB/B1NJ, PL/J, SJL/J, SWR/J, and 129P3/J) using a Go/No‐go task, which was designed to measure a subject’s ability to inhibit a behavior. Numerous aspects of response to ethanol and other drugs of abuse have been examined in these strains.Results: There were significant strain differences in the number of responses made during the No‐go signal (false alarms) and the extent to which strains responded differentially during the Go and No‐go signals (d′). The rate of responding prior to the cue did not differ among strains, although there was a statistically significant correlation between false alarms and precue responding that was not related to basal activity level. Interstrain correlations suggested that false alarms and rate of responding were associated with strain differences in ethanol‐related traits from the published literature.Conclusions: The results of this study do support a link between innate level of impulsivity and response to ethanol and are consistent with a genetic basis for some measures of behavioral inhibition.
Mapping Subchondral Bone Density of Selected Donor and Recipient Sites for Autologous Osteochondral Transplantation in the Canine Stifle Joint Using Computed Tomographic Osteoabsorptiometry
Authors: Böttcher Peter , Zeissler Markus , Grevel Vera , Oechtering Gerhard , Maierl Johann 
Published: May 2010

Objective: To characterize donor and recipient sites for autologous osteochondral transplantation (AOT) in the canine stifle joint with respect to maximal subchondral bone density (mSBD).Study Design: Descriptive laboratory study.Sample Population: Femora (n=15) of dogs (>20 kg).Methods: mSBD at selected donor sites within and outside the femoropatellar joint and at potential recipient sites for both femoral condyles was assessed using nonvolumetric computed tomographic osteoabsorptiometry and normalized to values obtained at the central weight‐bearing aspect of the lateral femoral condyle.Results: Only transplants harvested at the axial aspects of the lateral and medial trochlear ridge had a normalized mSBD comparable with the lateral and medial femoral condyle. Grafts from outside the femoropatellar joint, at the most proximal aspect of the medial femoral condyle and at the most distal aspect of the trochlea (the notch area) had mSBD values 13.8–24.4% less than at the femoral condyles.Conclusions: Choosing between donor sites within or outside the femoropatellar joint may significantly affect subchondral bone quality of harvested transplants.Clinical Relevance: Donor sites abaxial to the femoropatellar joint and at the most proximal aspect of the medial femoral condyle may provide transplants of suboptimal bone morphology, challenging their use as primary donor sites for AOT in dogs. However, this statement is based on nonvolumetric assessment of bone density, necessitating verification using volumetric density analysis to finally infer the biomechanical value of different grafts.
A functional AQP1 allele producing a Co(a–b–) phenotype revises and extends the Colton blood group system
Authors: Arnaud Lionel , Helias Virginie , Menanteau Cécile , Peyrard Thierry , Lucien Nicole , Ripoche Pierre , Lapègue Régine , Pham Bach‐Nga , Le Pennec Pierre‐Yves , Moulds John J. , Cartron Jean‐Pierre 
Published: May 2010

BACKGROUND: The Colton blood group system currently comprises three antigens, Coa, Cob, and Co3. The latter is only absent in the extremely rare individuals of the Colton “null” phenotype, usually referred to as Co(a–b–), which lack the water channel AQP1 that carries the Colton antigens. The discovery of a Co(a–b–) individual with no AQP1 deficiency suggested another molecular basis for the Co(a–b–) phenotype.STUDY DESIGN AND METHODS: Red blood cells were analyzed by stopped‐flow light scattering and Western blotting and typed by hemagglutination and flow cytometry. Genotyping by sequencing and polymerase chain reaction–restriction fragment length polymorphism was applied. An expression system for Colton antigens was developed in mammalian cells.RESULTS: Although Co(a–b–), the proband expressed fully functional AQP1 and had developed a novel Colton alloantibody. Sequencing of AQP1 revealed a homozygous nucleotide change (140A>G) encoding the single‐amino‐acid substitution Q47R. A second case was identified due to the presence of this novel Colton alloantibody. By generating an expression system for Colton antigens in K‐562 cells, the Q47R substitution was shown to inhibit the expression of both Coa and Cob antigens. Other naturally occurring single‐amino‐acid substitutions, that is, A45T, P38L, and N192K, were also studied in this Colton antigen expression system.CONCLUSIONS: The Co(a–b–) phenotype can be generated by a functional AQP1 allele, that is, AQP1 140G encoding AQP1 (Q47R) and allowing the development of a novel Colton alloantibody. This study also shows that the Cob antigen can be produced by at least two different substitutions at Amino Acid Position 45, that is, A45V and A45T.
Advanced glycation end products on stored red blood cells increase endothelial reactive oxygen species generation through interaction with receptor for advanced glycation end products
Authors: Mangalmurti Nilam S. , Chatterjee Shampa , Cheng Guanjun , Andersen Emily , Mohammed Aishat , Siegel Donald L. , Schmidt Ann Marie , Albelda Steven M. , Lee Janet S. 
Published: May 2010

BACKGROUND: Recent evidence suggests that storage‐induced alterations of the red blood cell (RBC) are associated with adverse consequences in susceptible hosts. As RBCs have been shown to form advanced glycation end products (AGEs) after increased oxidative stress and under pathologic conditions, we examined whether stored RBCs undergo modification with the specific AGE N‐(carboxymethyl)lysine (Nε‐CML) during standard blood banking conditions.STUDY DESIGN AND METHODS: Purified, fresh RBCs from volunteers were compared to stored RBCs (35‐42 days old) obtained from the blood bank. Nε‐CML formation was quantified using a competitive enzyme‐linked immunosorbent assay. The receptor for advanced glycation end products (RAGE) was detected in human pulmonary microvascular endothelial cells (HMVEC‐L) by real‐time polymerase chain reaction, Western blotting, and flow cytometry. Intracellular reactive oxygen species (ROS) generation was measured by the use of 5‐(and 6‐)chloromethyl‐2′,7′‐dichlorodihydrofluorescein diacetate, acetyl ester–based assays.RESULTS: Stored RBCs showed increased surface Nε‐CML formation when compared with fresh RBCs. HMVEC‐L showed detectable surface RAGE expression constitutively. When compared to fresh RBCs, stored RBCs triggered increased intracellular ROS generation in both human umbilical vein endothelial cells and HMVEC‐L. RBC‐induced endothelial ROS generation was attenuated in the presence of soluble RAGE or RAGE blocking antibody.CONCLUSIONS: The formation of the AGE Nε‐CML on the surface of stored RBCs is one functional consequence of the storage lesion. AGE‐RAGE interactions may be one mechanism by which transfused RBCs cause endothelial cell damage.
Patterns of Use of Topical Skin Adhesives in the Emergency Department
Authors: Singer Adam J. , Kinariwala Mira , Lirov Roy , Thode Jr. Henry C. 
Published: May 2010

AbstractObjectives:  The objective was to determine patterns of use of topical skin adhesives (TSA) for laceration repair. The authors hypothesized that TSA use would be more common in children and facial lacerations.Methods:  This was a structured retrospective chart review. The setting was a suburban, university‐based emergency department (ED) with an emergency medicine (EM) residency; the annual census is 85,000 visits. Charts from consecutive patients presenting with lacerations in the summer of 2008 (June 2008 through August 2008) were reviewed. Demographic, clinical, and wound characteristics were extracted from electronic medical records by trained investigators using structured data collection forms. Characteristics of lacerations repaired with TSA or other closure devices were compared with bivariate and multivariate analyses using odds ratios (ORs) and 95% confidence intervals (CIs).Results:  A total of 755 patients presented to the ED with lacerations over the study period, of whom primary closure was used in 667; nine were excluded because the method of closure was unknown. The most common methods of laceration closure were sutures (485), adhesives (88), and staples (86). Adhesives were used to close 27% of facial lacerations, compared to 4% of all other body locations (difference = 23%, 95% CI = 18% to 29%), and in 20% of pediatric versus 8% of adult lacerations (difference = 13%, 95% CI = 7% to 18%). Adjustment for other potential patient and wound characteristics showed that adhesives were more likely to be used to close facial lacerations (OR = 10.0 CI, 95% CI = 5.5 to 18.0) and lacerations in children (OR = 1.8, 95% CI = 1.1 to 3.0) and less likely to be used as laceration length increased (OR = 0.6, 95% CI = 0.4 to 0.8). Adhesive use was not statistically associated with patient sex or race, laceration edges or shape, or the need for deep sutures. Forty‐three percent of adhesive wounds were closed with no anesthetic, and a topical agent was used in another 48%. In contrast, a local anesthetic agent was injected in 87% of sutured wounds (p < 0.001) and 73% of stapled wounds (p < 0.001).Conclusions:  Topical skin adhesives are used more often for children, facial lacerations, and short lacerations. Use of adhesives may improve patient comfort as need for injecting a local anesthetic is reduced.ACADEMIC EMERGENCY MEDICINE 2010; 17:670–672 © 2010 by the Society for Academic Emergency Medicine