bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proteasome Inhibitor Lactacystin Induces Cholinergic Degeneration
Authors: Zhou Hai-Yan , Tan Yu-Yan , Wang Zhi-Quan , Wang Gang , Lu Guo-Qiang , Chen Sheng-Di 
Published: December 2014

Objective:Ubiquitin proteasome system dysfunction is believed to play an important role in the development of Parkinson's disease (PD), and almost all studies till now have mainly focused on the susceptibility of dopaminergic neurons to proteasome inhibition. However, in fact, there are many other types of neurons such as cholinergic ones involved in PD. In our present study, we attempt to figure out what effect the failure of ubiquitin proteasome function would execute on cholinergic cells in culture.Methods:We treated cholinergic cells in culture with various doses of lactacystin. Then MTT assay was used to evaluate the cellular viability and the Annexin V-PI method was used to detect apoptosis. Both cellular soluble and insoluble polyubiquitinated proteins were detected by western blot. Furthermore, the mitochondrial membrane potential was analyzed using JC-1 and the intracellular production of reactive oxygen species (ROS) was determined using the fluorescent probe CM-H2DCFDA.Results:We found that low doses of lactacystin were enough to induce significant apoptotic cell death, disturb the mitochondrial membrane potential, and cause oxidative stress. We also found that the amounts of polyubiquitinated proteins dramatically increased with high doses, although the loss of cells did not increase accordingly.Conclusions:Our results suggest that cholinergic cells are sensitive to ubiquitin proteasome system dysfunction, which exerts its toxic effect by causing mitochondrial dysfunction and subsequent oxidative stress, not through polyubiquitinated proteins accumulation.
Utility of Transcranial Doppler in Idiopathic Intracranial Hypertension
Authors: Hunter Gary , Voll Chris , Rajput Michele 
Published: December 2014

Introduction:Idiopathic intracranial hypertension (IIH) can be an elusive diagnosis, and poor visual outcomes may occur. Currently, the only means of accurately diagnosing and following these patients is with repeated lumbar puncture. Previous work has shown that transcranial doppler measurements of pulsatility correlate accurately with elevated intracranial pressure (ICP). This study is designed to assess whether pulsatility index (PI) correlates with ICP in patients newly diagnosed with IIH.Methods:Seven patients with clinical suspicion of IIH were included in this study. Clinical suspicion was based on history of recurrent headaches and papilledema. All patients had otherwise normal examinations and imaging. Middle cerebral arteries were insonated to obtain average PI values. Cerebrospinal fluid (CSF) was then withdrawn, and closing pressures were recorded. Pulsatility index values were then obtained again, within ten minutes after completing CSF withdrawal. PI values were correlated with ICP values, and pre and post CSF withdrawal values were compared.Results:All seven patients had elevated opening pressures (average 39 cm H2O, range 27-70). The average closing pressure after approximately 30 cc of CSF withdrawal was 11.9 cm H2O. The average PI before CSF withdrawal was 0.95, which dropped to 0.70 after CSF withdrawal (p = 0.02). The change in ICP was found to be correlated with a change in PI (p = 0.004).Conclusions:These findings suggest that PI may be useful for following patients with IIH non-invasively. Further study with larger groups and blinded assessments should be useful in better characterizing the accuracy of this technique.
Selection Bias Introduced by Neuropsychological Assessments
Authors: Olson Robert , Parkinson Maureen , McKenzie Michael 
Published: December 2014

Objective:Two prospective studies in patient with brain tumours were performed comparing the Mini Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). The first assessed their feasibility and the second compared their diagnostic accuracy against a four-hour neuropsychological assessment (NPA). The introduction of the NPA decreased accrual and retention rates. We were therefore concerned regarding potential selection bias.Methods:Ninety-two patients were prospectively accrued and subsequently divided into three categories: a) no NPA required b) withdrew consent to NPA c) completed NPA. In order to quantify any potential bias introduced by the NPA, patient demographics and cognitive test scores were compared between the three groups.Results:There were significant differences in age (p<0.001), education (p=0.034), dexamethasone use (p=0.002), MMSE (p=0.005), and MoCA scores (p<0.001) across the different study groups. Furthermore, with increasing involvement of the NPA, patients' cognitive scores and educational status increased, while their age, dexamethasone use, and opioid use all decreased. Individuals who completed the NPA had higher MoCA scores than individuals who were not asked to complete the NPA (24.7 vs. 20.5; p < 0.001). In addition, this relationship held when restricting the analyses to individuals with brain metastases (p < 0.001).Conclusions:In this study, the lengthy NPA chosen introduced a statistically and clinically significant source of selection bias. These results highlight the importance of selecting brief and well tolerated assessments when possible. However, researchers are challenged by weighing the improved selection bias associated with brief assessments at the cost of reduced diagnostic accuracy.
Increasing Use of Disease Modifying Drugs for MS in Canada
Authors: Rotstein Dalia L. , Mamdani Muhammad , O'Connor Paul W. 
Published: December 2014

Background/Objectives:The course of multiple sclerosis may be slowed by use of the disease modifying drugs (DMDs): subcutaneous or intramuscular interferon beta-1a, interferon beta-1b, glatiramer acetate, and natalizumab. We set out to compare utilization of these drugs in the Canadian provinces from 2002-2007.Methods:Using a retrospective cohort analysis, we reviewed population data from International Medical Statistics (IMS) Health between November 2001 and October 2007.Results:The total annual number of DMD prescriptions increased from 3.9, in 2002, to 5.1, in 2007, per 1,000 Canadians. The total annual cost of prescriptions rose from $187 million to $287 million. Of the four provinces responsible for the majority of prescriptions - Alberta, BC, Ontario, and Quebec - Quebec had the highest average annual prescription rate (7 per 1,000 population) and BC had the lowest rate (3.3 per 1,000 population). Subcutaneous interferon beta-1a was the most commonly used drug whereas glatiramer acetate showed the greatest growth in use from 2002 to 2007.Conclusions:Disease modifying drugs prescription rates and costs increased by more than 30% between 2002 and 2007. There was wide variation in DMD prescription rates and relative drug preferences across the provinces.
GPI-1046 Increases Presenilin-1 Expression and Restores NMDA Channel Activity
Authors: Steiner Joseph P. , Payne Kathryn B. , Main Christopher Drummond , D'Alfonso Sabrina , Jacobsen Kirsten X. , Hicks T. Philip , Staines William A. , Poulter Michael O. 
Published: December 2014

Background:Previously we showed that 6-hydroxydopamine lesions of the substantia nigra eliminate corticostriatal LTP and that the neuroimmunolophilin ligand (NIL), GPI-1046, restores LTP.Methods:We used cDNA microarrays to determine what mRNAs may be over- or under-expressed in response to lesioning and/or GPI-1046 treatment. Patch clamp recordings were performed to investigate changes in NMDA channel function before and after treatments.Results:We found that 51 gene products were differentially expressed. Among these we found that GPI-1046 treatment up-regulated presenilin-1 (PS-1) mRNA abundance. This finding was confirmed using QPCR. PS-1 protein was also shown to be over-expressed in the striatum of lesioned/GPI-1046-treated rats. As PS-1 has been implicated in controlling NMDA-receptor function and LTP is reduced by lesioning we assayed NMDA mediated synaptic activity in striatal brain slices. The lesion-induced reduction of dopaminergic innervation was accompanied by the near complete loss of NDMA receptor-mediated synaptic transmission between the cortex and striatum. GPI-1046 treatment of the lesioned rats restored NMDA-mediated synaptic transmission but not the dopaminergic innervation. Restoration of NDMA channel function was apparently specific as the sodium channel current density was also reduced due to lesioning but GPI-1046 did not reverse this effect. We also found that restoration of NMDA receptor function was also not associated with either an increase in NMDA receptor mRNA or protein expression.Conclusion:As it has been previously shown that PS-1 is critical for normal NMDA receptor function, our data suggest that the improvement of excitatory neurotransmission occurs through the GPI-1046-induced up-regulation of PS-1.
Scedosporium Cerebral Abscesses After Extra-Corporeal Membrane Oxygenation
Authors: Al-Jehani Hosam , Guiot Marie-Christine , Torres Carlos , Marcoux Judith 
Published: December 2014

Background:Scedosporial infections are usually encountered in the immunocompromised patients. However, they are now emerging in the immunocompetent population and have an affinity for the central nervous system. They represent a therapeutic challenge, since they are highly resistant to most antifungal medications.Methods:We report the case of an immunocompetent patient with multiple cerebral abscesses secondary toScedosporium apiospermumfollowing extracorporeal membrane oxygenation (ECMO) and review the literature about this challenging cerebral infection.Results:A previously healthy 33-year-old male admitted to the hospital for a community-acquired pneumonia requiring ECMO subsequently developed multiple cerebral abscesses. He was empirically treated with caspofungin, which was changed to voriconazole once surgical aspiration revealedScedosporium apiospermum.Despite multiple aspirations, decompressive craniectomy to alleviate intracranial pressure, and an appropriate antifungal agent, the patient did not survive this aggressive infection.Conclusion:Brain abscesses withScedosporium apiospermumpresent a therapeutic challenge. High clinical suspicion leading to early appropriate antifungal therapy and combined surgical interventions might improve the prognosis.
Glioblastoma Treatment in the Elderly in the Temozolomide Therapy Era
Authors: Coate Linda , McNamara Mairéad G. , Lwin Zarnie , MacFadden Derek , Al-Zahrani Ahmed , Massey Christine , Menard Cynthia , Millar Barbara Ann , Sahgal Arjun , Laperriere Normand , Mason Warren P. 
Published: December 2014

Background:Optimal treatment of glioblastoma (GBM) in the elderly remains unclear. The impact of age on treatment planning, toxicity, and efficacy at a Canadian Cancer Centre was retrospectively reviewed.Methods:Glioblastoma patients treated consecutively between 2004 and 2008 were reviewed. Utilizing 70 years as the threshold for definition of an elderly patient, treatments and outcome were compared in younger and elderly populations.Results:Four hundred and twenty one patients were included in this analysis and median overall survival (OS) for the entire cohort was 9.8 months. 290 patients were aged <70 (median age 57, range 17–69) and 131 were aged ≥70 (median age 76, range 70–93). Patients ≥70 were more likely to receive best supportive care (BSC) and all patients >70 who were treated with radiotherapy received <60 Gy (P<0.001), except one. Patients aged >70 demonstrated inferior survival (one year OS 16% versus 54% for those <70, HR 3.46, P<0.001). In patients treated with BSC only, age had no impact on survival (median survival two months in both groups, HR 0.89, P=0.75). For those treated with higher doses of radiotherapy (>30 Gy to <60 Gy), one year survival was 19% versus 24% in patients aged >70 versus <70 (HR 1.47, P=0.02) respectively.Conclusions:In this retrospective single institution series, elderly patients were more likely to be treated with BSC or palliative doses of radiotherapy. Randomized phase III study results are required for guidance in treatment of this population of patients.
Neurocognitive Changes in Tertiary Neurosyphilis: A Retrospective Chart Review
Authors: Beauchemin Philippe , Laforce Robert 
Published: December 2014

Context:Since the beginning of the new millennium, prevalence of syphilis has re-increased and is once again, a major public health problem. Neurosyphilis is the extension of syphilitic infection to the nervous system. It is considered by many as a cause of reversible dementia, when treated early. However, scarce data exist on the evolution of cognitive and behavioral impairments in patients affected by tertiary neurosyphilis.Objectives:The aim of this study was to explore the cognitive and behavioral changes in a cohort of patients diagnosed with neurosyphilis.Design:A retrospective study based on systematized chart review between 2000 and 2012 in a large neurological tertiary care facility.Outcome measure:Clinical evaluations by treating physicians.Results:Eighteen patients were identified with tertiary neurosyphilis. Out of this group, only two had systematic neuropsychological follow-up despite physician reports of significant and persistent cognitive and psychiatric changes. For these two cases, only slight improvements were noted in memory and executive skills while improvements in attention were marked. None of our patients had previous psychiatric history yet a large proportion developed symptoms after the infection.Conclusion:Although neurosyphilis is traditionally considered a reversible form of dementia, we found limited support for this claim in our two patients with close follow-up. Quality data on the cognitive and psychiatric changes in the rest of our cohort was dramatically lacking, and this could not be explained by absence of symptoms at presentation. Given the recrudescence of syphilis, we propose a systematic approach to the evaluation and follow-up of this disorder.
Kan injectivity in order-enriched categories
Authors: ADÁMEK JIŘÍ , SOUSA LURDES , VELEBIL JIŘÍ 
Published: December 2014

Continuous lattices were characterised by Martín Escardó as precisely those objects that are Kan-injective with respect to a certain class of morphisms. In this paper we study Kan-injectivity in general categories enriched in posets. As an example, ω-CPO's are precisely the posets that are Kan-injective with respect to the embeddings ω ↪ ω + 1 and 0 ↪ 1.For every class$\mathcal{H}$of morphisms, we study the subcategory of all objects that are Kan-injective with respect to$\mathcal{H}$and all morphisms preserving Kan extensions. For categories such asTop0andPos, we prove that whenever$\mathcal{H}$is a set of morphisms, the above subcategory is monadic, and the monad it creates is a Kock–Zöberlein monad. However, this does not generalise to proper classes, and we present a class of continuous mappings inTop0for which Kan-injectivity does not yield a monadic category.
Intergenerational risk-sharing through funded pensions and public debt
Authors: CHEN DAMIAAN H. J. , BEETSMA ROEL M. W. J. , PONDS EDUARD H. M. , ROMP WARD E. 
Published: December 2014

AbstractWe explore the benefits of intergenerational risk-sharing through both private funded pensions and via the public debt. We use a multi-period overlapping generation model with a pay-as-you-go pension pillar, a funded pension pillar and a government. Shocks are smoothed via the public debt and variations in the indexation of pension entitlements and pension contributions. The intensity of these adjustments increases when the pension funding ratio or public debt gets closer to their boundaries. The best-performing pension arrangement is a hybrid funded scheme in which both contributions and entitlement indexation are simultaneously deployed as stabilisation instruments. We find that contribution and indexation adjustment policies are substitutes and the same is the case for contribution and tax adjustment policies. By contrast, indexation and tax adjustment policies are complements. We compare different taxation regimes and conclude that a regime in which pension benefits are taxed, while contributions are paid before taxes, is preferred to a regime in which contributions are paid after taxes, but benefits are untaxed.
Life-cycle modification in open oceans accounts for genome variability in a cosmopolitan phytoplankton
Authors: von Dassow Peter , John Uwe , Ogata Hiroyuki , Probert Ian , Bendif El Mahdi , Kegel Jessica U , Audic Stéphane , Wincker Patrick , Da Silva Corinne , Claverie Jean-Michel , Doney Scott , Glover David M , Flores Daniella Mella , Herrera Yeritza , Lescot Magali , Garet-Delmas Marie-José , de Vargas Colomban 
Published: December 2014

Abstract
Emiliania huxleyi is the most abundant calcifying plankton in modern oceans with substantial intraspecific genome variability and a biphasic life cycle involving sexual alternation between calcified 2N and flagellated 1N cells. We show that high genome content variability in Emiliania relates to erosion of 1N-specific genes and loss of the ability to form flagellated cells. Analysis of 185 E. huxleyi strains isolated from world oceans suggests that loss of flagella occurred independently in lineages inhabiting oligotrophic open oceans over short evolutionary timescales. This environmentally linked physiogenomic change suggests life cycling is not advantageous in very large/diluted populations experiencing low biotic pressure and low ecological variability. Gene loss did not appear to reflect pressure for genome streamlining in oligotrophic oceans as previously observed in picoplankton. Life-cycle modifications might be common in plankton and cause major functional variability to be hidden from traditional taxonomic or molecular markers.
Identification of the remains of King Richard III
Authors: King Turi E. , Fortes Gloria Gonzalez , Balaresque Patricia , Thomas Mark G. , Balding David , Delser Pierpaolo Maisano , Neumann Rita , Parson Walther , Knapp Michael , Walsh Susan , Tonasso Laure , Holt John , Kayser Manfred , Appleby Jo , Forster Peter , Ekserdjian David , Hofreiter Michael , Schürer Kevin 
Published: December 2014

AbstractIn 2012, a skeleton was excavated at the presumed site of the Grey Friars friary in Leicester, the last-known resting place of King Richard III. Archaeological, osteological and radiocarbon dating data were consistent with these being his remains. Here we report DNA analyses of both the skeletal remains and living relatives of Richard III. We find a perfect mitochondrial DNA match between the sequence obtained from the remains and one living relative, and a single-base substitution when compared with a second relative. Y-chromosome haplotypes from male-line relatives and the remains do not match, which could be attributed to a false-paternity event occurring in any of the intervening generations. DNA-predicted hair and eye colour are consistent with Richard’s appearance in an early portrait. We calculate likelihood ratios for the non-genetic and genetic data separately, and combined, and conclude that the evidence for the remains being those of Richard III is overwhelming.
Pleiotropy of the de novo-originated gene MDF1
Authors: Li Dan , Yan Zhihui , Lu Lina , Jiang Huifeng , Wang Wen 
Published: December 2014

AbstractMDF1 is a young de novo-originated gene from a non-coding sequence in baker's yeast, S. cerevisiae, which can suppress mating and promote vegetative growth. Our previous experiments successfully demonstrated how Mdf1p binds to the key mating pathway determinant MATα2 to suppress mating. However, how Mdf1p promotes growth and fulfills the crosstalk between the yeast mating and growth pathways are still open questions. Thus, the adaptive significance of this new de novo gene remains speculative. Here, we show that Mdf1p shortens the lag phase of S. cerevisiae by physically interacting with SNF1, the governing factor for nonfermentable carbon source utilization and thereby confers a selective advantage on yeasts through the rapid consumption of glucose in the early generational stage in rich medium. Therefore, MDF1 functions in two important molecular pathways, mating and fermentation and mediates the crosstalk between reproduction and vegetative growth. Together, our results provide a comprehensive example of how a de novo-originated gene organizes new regulatory circuits and thereby confers a selective advantage on S. cerevisiae to allow exquisite adaptation to the changing environment.
La recherche de l’excellence en orthodontie de l’adulte :
entretien avec Bjørn U. Zachrisson
Authors: Zachrisson Bjørn U. , Amat Philippe 
Published: December 2014

Bjørn U. Zachrisson est Professeur Émérite au sein du Département d’Orthodontie de
l’Université d’Oslo (Norvège). Il conserve à Oslo une pratique libérale consacrée aux
traitements de l’adulte.
Il a rédigé plus de 270 articles cliniques et scientifiques,
publiés dans des revues internationales et dans des manuels d’orthodontie, de
parodontologie, de traumatologie et de dentisterie générale.
Il a représenté l’orthodontie
européenne à l’occasion de multiples congrès à travers le monde. Il a présenté de
nombreuses conférences magistrales et donné des cours pendant les congrès internationaux.
Bjørn U. Zachrisson a reçu toutes les récompenses essentielles en orthodontie, y compris
le prix Ketcham et Jaraback décerné par l’American Association of
Orthodontics. Il est co-rédacteur du Journal of Clinical
Orthodontics, rédacteur et auteur de «Ask an Expert» dans le World
Journal of Orthodontics. Il collabore à l’Editorial Board of the
Seminars in Orthodontics, à l’Angle Orthodontist, au
World Journal of Orthodontics, à la Revista Dental Press de
Ortodontia e Ortopedia and Revista Clinica de Ortodontia (Brésil), à
l’Italian Journal of Orthodontics, ainsi qu’à l’European
Journal of Esthetic Dentistry.
Social, institutional, and knowledge mechanisms mediate diverse ecosystem service benefits from coral reefs
Authors: Hicks Christina C. , Cinner Joshua E. 
Published: December 2014

Significance
Ecosystems provide a range of services that can benefit people. However, the extent to which people are able to harness those benefits depends not only on the supply of ecosystem services but also on their capacity to access them via a range of social, economic, and institutional mechanisms. Here, we examine how people perceive ecosystem service benefits across 28 coral reef fishing communities in four countries. We quantitatively show that bundles of benefits are mediated by key access mechanisms (e.g., rights-based, economic, knowledge, social, and institutional). Interestingly, social, institutional, and knowledge mechanisms were associated with the greatest number and diversity of benefits. Resource managers can focus on these access mechanisms to maximize ecosystem service benefits while minimizing human–environment impacts.