bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pre‐synaptic defects of NPC1‐deficient hippocampal neurons are not directly related to plasma membrane cholesterol
Authors: Hawes Cory M. , Wiemer Hana , Krueger Stefan R. , Karten Barbara 
Published: April 2010

J. Neurochem. (2010) 114, 311–332.AbstractImbalances in brain cholesterol homeostasis have been observed in several neurodegenerative diseases. In Niemann‐Pick Type C (NPC) disease, mutations in NPC1 or NPC2 lead to endosomal cholesterol accumulation, neuronal dysfunction and death. Cholesterol in synaptic plasma membranes influences membrane fluidity, curvature, and protein function, and its depletion may adversely affect synaptic vesicle cycling. We have investigated pre‐synaptic function in primary hippocampal neurons with altered cholesterol distribution because of NPC1 deficiency or cyclodextrin treatment. In NPC1‐deficient neurons grown in serum‐free medium, plasma membrane cholesterol was reduced and total synaptic vesicle release during prolonged stimulation was attenuated. In NPC1‐deficient neurons cultured in the presence of high‐density lipoproteins, plasma membrane cholesterol markedly increased, but the defects in synaptic vesicle release in NPC1‐deficient neurons were exacerbated. Treatment with 1 mM methyl‐β‐cyclodextrin acutely depleted plasma membrane cholesterol in wild‐type neurons to levels below those in NPC1 deficiency, but did not alter synaptic vesicle exo‐ or endocytosis. Defects only became apparent when higher methyl‐β‐cyclodextrin concentrations were used. Our data indicate that synaptic vesicle release can tolerate some degree of plasma membrane cholesterol depletion and suggest that the pre‐synaptic defects in NPC1‐deficient neurons are not solely caused by a reduction of plasma membrane cholesterol.
Dyrk1A‐mediated phosphorylation of Presenilin 1: a functional link between Down syndrome and Alzheimer’s disease
Authors: Ryu Young Shin , Park So Young , Jung Min‐Su , Yoon Song‐Hee , Kwen Mi‐Yang , Lee Sun‐Young , Choi Sun‐Hee , Radnaabazar Chinzorig , Kim Mi‐Kyoung , Kim Hangun , Kim Kwonseop , Song Woo‐Joo , Chung Sul‐Hee 
Published: April 2010

J. Neurochem. (2010) 115, 574–584.AbstractThe dual‐specificity tyrosine(Y)‐phosphorylation‐regulated kinase 1A (Dyrk1A) gene is located on human chromosome 21 and encodes a proline‐directed protein kinase that might be responsible for mental retardation and early onset of Alzheimer’s disease (AD) in Down syndrome (DS) patients. Presenilin 1 (PS1) is a key component of the γ‐secretase complex in the generation of β‐amyloid (Aβ), an important trigger protein in the pathogenesis of AD. Increased Dyrk1A expression has been reported in human AD and DS brains. We previously showed that Dyrk1A increased Aβ production in mammalian cells and transgenic mice that over‐express Dyrk1A. In this study, we describe a potential mechanism by which Aβ is increased in Dyrk1A‐over‐expressing DS and AD brains. First, we show that PS1 is phosphorylated by the Dyrk1A at Thr354 and that this phosphorylation increases γ‐secretase activity. Then, using transgenic mice that over‐express human Dyrk1A, we demonstrate that phospho‐Thr354‐PS1 (pT354‐PS1) expression is enhanced when Dyrk1A level is increased. We also show that pT354‐PS1 is more stable than the unphosphorylated form of PS1. These results reveal a potential regulatory link between Dyrk1A and PS1 in the Aβ pathway of DS and AD brains, suggesting that up‐regulated Dyrk1A may accelerate AD pathogenesis through PS1 phosphorylation.
17β‐Estradiol protects Schwann cells against H2O2‐induced cytotoxicity and increases transplanted Schwann cell survival in a cervical hemicontusion spinal cord injury model
Authors: Siriphorn Akkradate , Chompoopong Supin , Floyd Candace L. 
Published: April 2010

J. Neurochem. (2010) 115, 864–872.AbstractSchwann cell (SC) transplantation is a promising repair strategy after spinal cord injury (SCI); however, a large number of SCs do not survive following transplantation. Previous studies have shown that 17β‐estradiol (E2) protects several cell types against cytotoxicity. Thus, this study evaluated the protective potential of E2 on SCs in vitro and investigated the effect of E2 on transplanted SC survival in a rat model of SCI. Primary SC cultures were found to robustly express estrogen receptors (ER) and incubation with E2 protected SCs against hydrogen peroxide‐induced cell death. This protection was not inhibited by the ER antagonist ICI 182,780, suggesting that genomic signaling is not necessary for protection. In a subsequent experiment, cervical hemicontusion SCI was induced in male rats followed by sustained administration of E2 or placebo. Eight days after SCI, SCs were transplanted into the injury epicenter. E2 treatment significantly increased the number of surviving labeled transplanted SCs evaluated 7 days after transplantation. These data demonstrate that E2 protects SCs against oxidative stress and improves transplanted SC survival, which suggests that E2 administration may be an intervention of choice for enhancing survival of transplanted SCs after SCI.
Manganese chelation therapy extends survival in a mouse model of M1000 prion disease
Authors: Brazier Marcus W. , Volitakis Irene , Kvasnicka Magda , White Anthony R. , Underwood John R. , Green Jason E. , Han Sen , Hill Andrew F. , Masters Colin L. , Collins Steven J. 
Published: April 2010

J. Neurochem. (2010) 114, 440–451.AbstractPrevious in vitro and in vivo investigations have suggested manganese (Mn2+) may play a role in pathogenesis through facilitating refolding of the normal cellular form of the prion protein into protease resistant, pathogenic isoforms (PrPSc), as well as the subsequent promotion of higher order aggregation of these abnormal conformers. To further explore the role of Mn2+ in pathogenesis, we undertook a number of studies, including an assessment of the disease modifying effects of chelation therapy in a well‐characterized mouse model of prion disease. The di‐sodium, calcium derivative of the chelator, cyclohexanediaminetetraacetic acid (Na2CaCDTA), was administered intraperitoneally to mice inoculated intra‐cerebrally with either high or low‐dose inocula, with treatment beginning early (shortly after inoculation) or late (at the usual mid‐survival point of untreated mice). Analyses by inductively coupled plasma‐mass spectrometry demonstrated brain Mn2+ levels were selectively reduced by up to 50% in treated mice compared with untreated controls, with copper, iron, zinc and cobalt levels unchanged. In mice administered high‐dose inocula, none of the treatment groups displayed an increase in survival although western blot analyses of early intensively treated mice showed reduced brain PrPSc levels; mice infected using low‐dose inocula however, showed a significant prolongation of survival (p = 0.002). Although our findings support a role for Mn2+ in prion disease, further studies are required to more precisely delineate the extent of pathogenic involvement.
The microbe–mineral environment and gypsum neogenesis in a weathered polar evaporite
Authors: COCKELL C. S. , OSINSKI G. R. , BANERJEE N. R. , HOWARD K. T. , GILMOUR I. , WATSON J. S. 
Published: April 2010

AbstractEvaporitic deposits are a globally widespread habitat for micro‐organisms. The microbe–mineral environment in weathered and remobilized gypsum from exposed mid‐Ordovician marine evaporite beds in the polar desert of Devon Island, Nunavut, Canadian High Arctic was examined. The gypsum is characterized by internal green zones of cyanobacterial colonization (dominated by Gloeocapsa/Aphanothece and Chroococcidiopsis spp. morphotypes) and abundant black zones, visible from the surface, that contain pigmented cyanobacteria and fungi. Bioessential elements in the gypsum are primarily provided by allochthonous material from the present‐day polar desert. The disruption, uplift and rotation of the evaporite beds by the Haughton meteorite impact 39 Ma have facilitated gypsum weathering and its accessibility as a habitat. No cultured cyanobacteria, bacteria and fungi were halophilic consistent with the expectation that halophily is not required to persist in gypsum habitats. Heterotrophic bacteria from the evaporite were slightly or moderately halotolerant, as were heterotrophs isolated from soil near the gypsum outcrop showing that halotolerance is common in arctic bacteria in this location. Psychrotolerant Arthrobacter species were isolated. No psychrophilic organisms were isolated. Two Arthrobacter isolates from the evaporite were used to mediate gypsum neogenesis in the laboratory, demonstrating a potential role for microbial biomineralization processes in polar environments.
Surface wetness and mire development during the late Holocene in central Sweden
Authors: ANDERSSON SOFIA , SCHONING KRISTIAN 
Published: April 2010

Andersson, S. & Schoning, K. 2010: Surface wetness and mire development during the late Holocene in central Sweden. Boreas, Vol. 39, pp. 749–760. 10.1111/j.1502‐3885.2010.00157.x. ISSN 0300‐9483.Late Holocene mire development and surface wetness changes have been studied in a small mixed mire located in central Sweden. Today the mire is characterized by a mainly ombrotrophic centre dominated by Sphagnum mosses, with Carex content increasing towards the more minerotrophic mire margins. Two peat sequences extracted from the central ombrotrophic part were investigated for stratigraphy, humification, testate amoebae analysis, C/N ratio and δ13C and δ15N stable isotopes. Three main stages of mire development are identified, with the first stage, between c. 4200 and 2600 cal. yr BP, characterized by water‐logged conditions, suggesting a minerotrophic fen stage. The second stage, between c. 2600 and 1000 cal. yr BP, is characterized by more ombrotrophic conditions and Sphagnum‐dominated vegetation. The onset of the prominent change at c. 2600 cal. yr BP could have been initiated by climate change coincident with a change in solar activity. The last stage, between c. 1000 and 50 cal. yr BP, is dominated by more ombrotrophic conditions, suggesting increased precipitation. This study shows that the response of hydrological proxies in a mixed mire during its development towards more ombrotrophic conditions might result in conflicting results, a finding that needs to be considered in palaeoenvironmental reconstructions from mires that change between ombrotrophic and minerotrophic settings.
Long‐Term, Open‐Label Safety Study of Oral Almotriptan 12.5 mg for the Acute Treatment of Migraine in Adolescents
Authors: Berenson Frank , Vasconcellos Elza , Pakalnis Ann , Mao Lian , Biondi David M. , Armstrong Robert B. 
Published: April 2010

(Headache 2010;50:795‐807)Objectives.— This study evaluated the long‐term safety of oral almotriptan 12.5 mg for the treatment of multiple migraine episodes in adolescents over a 12‐month period. Efficacy outcomes were assessed as a secondary objective.Methods.— Adolescent migraineurs aged 12‐17 years were enrolled in this 12‐month, open‐label study (Study ID CR002827). Patients were instructed to record their assessments on paper headache records whenever they experienced a migraine headache that they treated with study medication. Safety was assessed descriptively and assessments included adverse event (AE) recording, change in laboratory values, vital signs, and electrocardiogram parameters. Efficacy outcomes were assessed descriptively and outcomes included rates for 2‐ and 24‐hour pain relief and sustained pain relief, 2‐ and 24‐hour pain‐free and sustained pain‐free, and presence of migraine‐associated symptoms of photophobia, phonophobia, nausea and vomiting.Results.— Overall, 67.1% of patients reported ≥1 AE over the course of the trial, 7.6% had an AE judged by the study investigator to be related to treatment with almotriptan, 2.4% discontinued because of an AE, and 1.9% reported serious AEs. The most commonly reported treatment‐related AEs (occurring in ≥1% of patients) were nausea (1.4%) and somnolence (1.4%). Pain relief responses for treated migraines of moderate or severe intensity at baseline were 61.7% and 68.6%, at 2 and 24 hours, respectively; the sustained pain relief rate was 55.5%. Pain‐free responses were reported for 40.5% of all treated migraines at 2 hours and 65.9% of treated migraines at 24 hours; the sustained pain‐free rate was 38.4%. The proportion of migraines that achieved the pain relief, sustained pain relief, pain‐free and sustained pain‐free endpoints were similar in the 12‐ to 14‐year and 15‐ to 17‐year age groups. Treating with almotriptan 12.5 mg when headache pain was mild was associated with higher rates of pain relief and pain‐free at 2 and 24 hours, and sustained pain relief and sustained pain‐free, compared with treatment initiated when pain was severe.Conclusions.— Almotriptan 12.5 mg was well tolerated in this adolescent population over a 12‐month period. No unexpected safety or tolerability concerns were revealed over the course of this study. The results are consistent with almotriptan 12.5 mg being effective for the acute treatment of pain and symptoms associated with migraine in both younger and older adolescents.
Evaluation of the Abrasiveness of Dentifrices for Complete Dentures
Authors: Pisani Marina Xavier , Bruhn Juliana Pascotti , Paranhos Helena Freitas Oliveira , Silva‐Lovato Cláudia Helena , De Souza Raphael Freitas , Panzeri Heitor 
Published: April 2010

Abstract Purpose: This study analyzed the surface roughness and weight loss in Plex Glass specimens caused by dentifrices, one conventional (Sorriso) and three specific for dentures. Materials and Methods: Specimens (n = 6) of Plex Glass were divided into 5 groups including: negative control (water); positive control 1 (Sorriso) and 2 (Corega Brite); Experimental 1 (containing Chloramine T, antimicrobial agent); and Experimental 2 (containing Zonyl, detergent). Brushing was performed in a toothbrushing machine (Pepsodent) with a soft brush and a suspension of toothpaste and distilled water for 300 minutes, representing 6 years of brushing. Weight was measured initially and after the trial period; roughness was measured after the trial period only. The results of roughness and weight loss were analyzed using ANOVA and Tukey tests at 5%. Results: The negative control (2.82 ± 4.41 mg) showed the lowest weight loss. Experimental 1 (13.62 ± 4.29 mg) and Experimental 2 (15.4 ± 5.80 mg) were equal statistically, and Sorriso (23.22 ± 7.23 mg) and Corega (28.83 ± 6.34 mg) produced the greatest weight loss. Concerning roughness, the negative control group (0.03 ± 0.01 μm) showed the lowest value. No significant differences were found between Corega (13.43 ± 1.65 μm), Experimental 1 (12.28 ± 0.85 μm), and Experimental 2 (10.68 ± 2.56 μm). The Sorriso toothpaste produced the greatest amount of surface roughness (19.15 ± 2.36 μm). Conclusion: Of the tested dentifrices, the experimental preparations proved to be the least abrasive and resulted in the lowest weight loss after brushing of the acrylic. Based on these findings, the use of these experimental dentifrices is advocated. Further evaluation based on the ability of these preparations to remove biofilms is required.
Management of acute anemia in a Jehovah's Witness patient with acute lymphoblastic leukemia with polymerized bovine hemoglobin‐based oxygen carrier: a case report and review of literature
Authors: Donahue Laura L. , Shapira Iuliana , Shander Aryeh , Kolitz Jonathan , Allen Steven , Greenburg Gerson 
Published: April 2010

BACKGROUND: Management of severe symptomatic anemia is exceptionally challenging when blood transfusions cannot be administered. Use of hemoglobin (Hb)‐based oxygen carriers as “bridging treatment” can be an option.CASE REPORT: This is a report of a 36‐year‐old Jehovah's Witness diagnosed with acute lymphoblastic leukemia (ALL) who developed severe symptomatic anemia (Hb as low as 3.1 g/dL) during induction chemotherapy and refused allogeneic blood transfusions. Fifteen units of Hemopure (Biopure Corp.), an investigational polymerized bovine Hb‐derived artificial oxygen carrier, were administered over a 12‐day period after informed consent was obtained. The patient's condition improved.RESULTS: Chart review was performed to identify relevant information about the patient's clinical status during Hemopure treatment. With the use of Hemopure the patient's total Hb level was maintained between 3.6 and 5.3 g/dL, over a 12‐day period, without any evidence of ischemia or organ dysfunction indicating that Hemopure was providing adequate tissue oxygen supply until marrow red blood cell recovery. The patient completed the chemotherapy regimen and was discharged in stable condition and has been in remission for 28 months.CONCLUSION: This report documents the successful management of profound anemia in an acute leukemia patient who refused blood transfusion, with the use of Hemopure, to save the patient from the devastating effects of ischemia associated with severe anemia. Hemopure may represent a life‐saving intervention in patients with severe symptomatic anemia when blood transfusion is not an option.
The influence of conditions utilized to hold apheresis and whole blood–derived platelet samples before platelet enumeration with three hematology analyzers
Authors: Seetharaman Shalini , Kline Linda , Dabay Michelle , Kurtz James , Moroff Gary 
Published: April 2010

BACKGROUND: The Advia 120 (Siemens Diagnostics) hematology analyzer is different from other hematology analyzers in that it requires platelets (PLTs) to be “effectively spherical” to be counted. Our study evaluated how PLT counts with this hematology analyzer and two other models were influenced by the holding of PLT product samples.STUDY DESIGN AND METHODS: Samples were prepared from apheresis PLT products (APs) collected in ACD‐A and from whole blood–derived PLT concentrates (PCs) in CP2D or ACD‐A. Samples were stored in K2 and K3ethylenediaminetetraacetate (EDTA) tubes at room temperature (RT) and in the cold. PLT counts were determined immediately, after 1 and 4 hours, and after an overnight hold, using Advia 120, XE‐2100D, and Cell‐Dyn 3700 hematology analyzers.RESULTS: A time‐dependent increase in PLT counts was observed with AP samples held at RT using the Advia 120, but not with the other two hematology analyzers. AP samples held in the cold did not show a substantial time‐dependent increase with any of the hematology analyzers. With the Advia 120, the PLT counts in the immediate samples were approximately 14% lower compared to those in cold or overnight‐held RT samples. PC samples with all holding conditions and hematology analyzers did not show any substantial time‐dependent increase in counts.CONCLUSIONS: With the Advia 120 hematology analyzer, the time‐dependent increase in PLT counts with RT‐held samples may be related to the need to have effectively sphered PLTs unlike that with the other two hematology analyzers. The absence of a holding effect with PC samples may indicate that only AP samples have population(s) that are slow to convert to spherical PLTs.
The detection of platelet antibodies by simultaneous analysis of specific platelet antibodies and the monoclonal antibody–specific immobilization of platelet antigens: an interlaboratory comparison
Authors: Nguyen Xuan Duc , Goebel Meike , Schober Michael , Klüter Harald , Panzer Simon 
Published: April 2010

BACKGROUND: Glycoprotein (GP)‐specific platelet (PLT) antibodies can cause allo‐ or autoimmune thrombocytopenia. Their detection is of high diagnostic value. The simultaneous analysis of specific PLT antibodies (SASPA) assay is based on simultaneous detection of various PLT‐specific antibodies by flow cytometry and has entered routine use in our Mannheim institution. In this study, we performed an interlaboratory comparison investigation of PLT‐specific antibodies using SASPA versus the “gold standard,” the monoclonal antibody–specific immobilization of PLT antigen (MAIPA) assay.STUDY DESIGN AND METHODS: Sera from 194 patients with suspected PLT allo‐ or autoantibodies were tested against GPIIb/IIIa, IX, Ia/IIa, IV, and HLA Class I by SASPA (in Mannheim) and MAIPA (in Vienna). All data were reported blinded to those from the respective other method. Sensitivity studies included dilution studies with known antibodies against HPA‐1a, ‐1b, ‐3b, ‐5b, and ‐15b and HLA Class I.RESULTS: Overall, results were concordant in 78.9%. The specificity and sensitivity of SASPA, based on the MAIPA results, were 97.3 and 86.3%, respectively, for the detection of alloantibodies. The respective results for the detection of autoantibodies were 95.3 and 44.9%. Serial dilution experiments with sera containing anti‐HPA1a, ‐1b, ‐3b, ‐5b, and ‐15b and anti‐HLA Class I revealed a higher sensitivity of the SASPA assay with all alloantibodies.CONCLUSION: In this first blind interlaboratory comparison, SASPA yielded similar results to those of MAIPA. The SASPA assay may be superior to the MAIPA assay for the detection of weak alloantibodies while simultaneous detection of a variety of antibody specificities or immunoglobulin classes and the need of fewer PLTs are obvious advantages.
The seroprevalence of hepatitis C virus (HCV) among 559,890 first‐time volunteer blood donors in China reflects regional heterogeneity in HCV prevalence and changes in blood donor recruitment models
Authors: Fu Yongshui , Xia Wenjie , Wang Yizhong , Tian Linwei , Pybus Oliver G. , Lu Ling , Nelson Kenrad 
Published: April 2010

BACKGROUND: A decrease in the prevalence of hepatitis C virus antibody (anti‐HCV) has been reported among voluntary blood donors in some regions of China. However, the prevalence of HCV among volunteer blood donors in other regions of China has not been reported. The aim of this study was to investigate the seroprevalence of HCV among 559,890 first‐time volunteer blood donors recruited during 2004 through 2007 at the Guangzhou Blood Center, China.STUDY DESIGN AND METHODS: Anti‐HCV was detected using two different third‐generation enzyme immunoassay kits. HCV RNA was detected using reverse transcription–polymerase chain reaction (RT‐PCR) targeting the 5′‐untranslated region of HCV.RESULTS: Among 559,890 donors, 1877 (0.335%) were positive for anti‐HCV. The anti‐HCV+ rate was significantly higher in males than females (0.37% vs. 0.28%; p < 0.001) and significantly lower among donors living in Guangdong Province than donors who had migrated from other locations (0.30% vs. 0.40%; p < 0.001). Among the 1877 anti‐HCV+ donors, 450 were randomly selected for HCV nucleic acid amplification by RT‐PCR. Of these, 270 (60%) were HCV RNA+ and 180 (40%) were HCV RNA−.CONCLUSIONS: Many donors from outside Guangdong Province were migrant laborers from other areas in China, suggesting that there is regional heterogenicity in HCV prevalence within China. The overall anti‐HCV+ rate reported here is among the lowest reported among blood donors in China reflecting the effect of the current recruitment of exclusively volunteer donors.