bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variation in the nitrogen isotopic composition of amino acids in benthic foraminifera: Implications for their adaptation to oxygen‐depleted environments
Authors: Nomaki Hidetaka , Chikaraishi Yoshito , Tsuchiya Masashi , Toyofuku Takashi , Suga Hisami , Sasaki Yoko , Uematsu Katsuyuki , Tame Akihiro , Ohkouchi Naohiko 
Published: July 2015

AbstractWe evaluated nitrate utilization by benthic foraminifera at the redox boundary around the sediment‐water interface by examining the stable nitrogen isotopic composition (δ15N, ‰ vs. AIR) of amino acids. Five foraminiferal species collected from bathyal Sagami Bay (water depth, 1430 m) in three different sampling seasons were analyzed by determining the δ15N values of amino acids from whole cells and those in test (shell) proteins remaining after H2O2 treatment. The δ15N values of phenylalanine fell within a narrow range (typically 1–3‰) in the test proteins of all five species, but the whole‐cell δ15N values of phenylalanine were substantially different from those of the test proteins in two species, Globobulimina affinis (by 6.3‰) and Uvigerina akitaensis (by 4.5‰). These differences in the δ15N values of amino acids suggest that these species utilize nitrate in their cells probably for nitrate respiration (i.e., denitrification) to adapt to oxygen‐depleted environments, as was previously observed in the shallow water benthic foraminifera Ammonia sp. Apparent trophic positions determined using the δ15N values of amino acids also differed between whole cells and tests in G. affinis, U. akitaensis, and Ammonia sp., perhaps because they have different microbial associations, as observed by cellular ultrastructural analysis. These differences in nitrate utilization and microbial associations among benthic foraminifera suggest that foraminifera adapt in diverse ways to conditions in dysoxic to anoxic sediments.
Olfaction in Homozygous and Heterozygous SYNJ1 Arg258Gln Mutation Carriers
Authors: Picillo Marina , De Rosa Anna , Pellecchia Maria Teresa , Criscuolo Chiara , Amboni Marianna , Erro Roberto , Bonifati Vincenzo , De Michele Giuseppe , Barone Paolo 
Published: July 2015

AbstractHyposmia is a common nonmotor symptom in Parkinson's disease (PD) and has been variably detected in monogenic parkinsonism. SYNJ1 has been recently identified as the gene defective in a novel form of autosomal‐recessive, early‐onset atypical parkinsonism, designed as PARK20. To assess olfaction in PARK20, we administered the University of Pennsylvania Smell Identification Test (UPSIT) in four groups of subjects: SYNJ1 homozygous (HOM = 3) and heterozygous (HET = 4); sporadic PD (PD = 68); and healthy control subjects (CTR = 61). A linear regression model was constructed to assess the association between raw UPSIT score (outcome) and group (HOM, HET, PD, and CTR), adjusting for age, gender, and current smoking status. Likewise in PD patients, odor identification is impaired in homozygous SYNJ1 mutation carriers. Although the limited sample size precludes definite conclusions about olfaction in SYNJ1‐related parkinsonism, our findings suggest new insights into PARK20 phenotype and pathophysiology.
Estimating the Proportion of Essential Tremor and Parkinson's Disease Patients Undergoing Deep Brain Stimulation Surgery: Five‐Year Data From Columbia University Medical Center (2009–2014)
Authors: Kestenbaum Meir , Ford Blair , Louis Elan D. 
Published: July 2015

AbstractObjectiveThe aim of this study was to estimate, at a tertiary referral center, the proportion of essential tremor (ET) and Parkinson's disease (PD) patients who underwent DBS surgery.BackgroundDBS surgery is an important treatment for ET and PD. Surprisingly, there are no published data on the precise proportion of such patients who are referred for this procedure.MethodsUsing the computerized billing database at the Center for Parkinson's Disease and Other Movement Disorders, Columbia University Medical Center, we searched for patients who received the diagnostic codes 333.1 (tremor) and 332.0 (PD) and who were followed by a doctor at the center during the 5‐year period from 2009 to 2014. The number of patients who underwent DBS surgery for these diagnoses during this time period was also determined.ResultsSeventy‐seven patients with these diagnoses (52 PD, 14 ET, and 11 ET + PD) who were followed at the center underwent DBS surgery during this time period. The proportion of ET patients who underwent DBS surgery was 2.90% (95% confidence interval [CI]: 1.78–4.02), and for PD this was 1.38% (95% CI: 1.04–1.72). The difference was significant (P < 0.001).ConclusionsAt a tertiary‐referral center, 1 in 34 ET patients and 1 in 72 PD patients underwent DBS surgery. Similar studies from other major centers would be of additional value. These data are likely to have utility when planning health care services for patients with these diagnoses.
Adenosine 2A Receptor Antagonists for the Treatment of Motor Symptoms in Parkinson's Disease
Authors: Pourcher Emmanuelle , Huot Philippe 
Published: July 2015

AbstractBackgroundTreatment of motor fluctuations in Parkinson's disease (PD) remains an unmet challenge. Adenosine 2A (A2A) receptors are located along the indirect pathway and represent a potential target to enhancel‐3,4‐dihydroxyphenylalanine (l‐DOPA) antiparkinsonian action.MethodsThis article summarizes the preclinical and clinical literature on A2Aantagonists inPD, with a specific focus on their effect onofftime,ontime, and dyskinesia.FindingsSeveral A2Areceptor antagonists have been tested in preclinical studies and clinical trials. In preclinical studies, A2Aantagonists enhancedl‐DOPAantiparkinsonian action without exacerbating dyskinesia, but A2Aantagonists were generally administered in combination with a subthreshold dose ofl‐DOPA, which is different to the paradigms used in clinical trials, where A2Aantagonists were usually added to an optimal antiparkinsonian regimen. In clinical settings, A2Aantagonists generally reduced duration ofofftime, by as much as 25% in some studies. The effect ofontime duration is less clear, and in a few studies an exacerbation of dyskinesia was reported. Two A2Aantagonists have been tested in phaseIIIsettings: istradefylline and preladenant. Istradefylline was effective in two phaseIIItrials, but ineffective in another; the drug has been commercially available in Japan since 2013. In contrast, preladenant was ineffective in a phaseIIItrial and the drug was discontinued. A phaseIIIstudy with tozadenant will begin in 2015; the drug was effective at reducingofftime in a phaseIIb study. Other A2Aantagonists are in development at the preclinical and early clinical levels.
Corticobasal Syndrome in a Family with Early‐Onset Alzheimer's Disease Linked to a Presenilin‐1 Gene Mutation
Authors: Navarro Eloisa , De Andrés Clara , Guerrero Carmen , Giménez‐Roldán Santiago 
Published: July 2015

AbstractBackgroundAlzheimer's disease (AD) is the second‐most frequent cause underlying corticobasal syndrome (CBS). However, a reliable diagnosis using clinical, neuropsychological, or neuroimaging approaches has not yet been achieved.MethodsClinical, neuropsychological, imaging, and neuropathology studies were undertaken in a large Spanish family with early‐onset familial AD (EOFAD) carrying a Met233Leu mutation linked to presenilin‐1 gene (PSEN‐1).ResultsTwo of three examined members of this family presented with the usual amnestic pattern. At the age of 47 years, a third family member, in whom pathology was later confirmed, developed prominent CBS combined with severe neuropsychiatric and behavioral disturbances resembling those often found in EOFAD.ConclusionAlthough CBS in EOFAD appears to be rare, demonstration of a linkage to PSEN‐1 gene mutations may permit in vivo diagnosis.
Improving the development of early bovine somatic‐cell nuclear transfer embryos by treating adult donor cells with vitamin C
Authors: Chen Huanhuan , Zhang Lei , Guo Zekun , Wang Yongsheng , He Rongjun , Qin Yumin , Quan Fusheng , Zhang Yong 
Published: July 2015

SUMMARYVitamin C (Vc) has been widely studied in cell and embryo culture, and has recently been demonstrated to promote cellular reprogramming. The objective of this study was to identify a suitable Vc concentration that, when used to treat adult bovine fibroblasts serving as donor cells for nuclear transfer, improved donor‐cell physiology and the developmental potential of the cloned embryos that the donor nuclei were used to create. A Vc concentration of 0.15 mM promoted cell proliferation and increased donor‐cell 5‐hydroxy methyl cytosine levels 2.73‐fold (P < 0.05). The blastocyst rate was also significantly improved after nuclear transfer (39.6% treated vs. 26.0% control, P < 0.05); the average number of apoptotic cells in cloned blastocysts was significantly reduced (2.2 vs. 4.4, P < 0.05); and the inner cell mass‐to‐trophectoderm ratio (38.25% vs. 30.75%, P < 0.05) and expression of SOX2 (3.71‐fold, P < 0.05) and POU5F1 (3.15‐fold, P < 0.05) were significantly increased. These results suggested that Vc promotes cell proliferation, decreases DNA methylation levels in donor cells, and improves the developmental competence of bovine somatic‐cell nuclear transfer embryos. Mol. Reprod. Dev. 82: 867–879, 2015. © 2015 Wiley Periodicals, Inc.
Deletion of low molecular weight protein tyrosine phosphatase (Acp1) protects against stress‐induced cardiomyopathy
Authors: Wade Fallou , Quijada Pearl , Al‐Haffar Kamar Mohamed Adib , Awad Salma Mahmoud , Kunhi Muhammad , Toko Haruhiro , Marashly Qussay , Belhaj Karim , Zahid Israa , Al‐Mohanna Falah , Stanford Stephanie M , Alvarez Roberto , Liu Yingge , Colak Dilek , Jordan Maria C , Roos Kenneth P , Assiri Abdullah , Al‐Habeeb Waleed , Sussman Mark , Bottini Nunzio , Poizat Coralie 
Published: July 2015

AbstractThe low molecular weight protein tyrosine phosphatase (LMPTP), encoded by the ACP1 gene, is a ubiquitously expressed phosphatase whose in vivo function in the heart and in cardiac diseases remains unknown. To investigate the in vivo role of LMPTP in cardiac function, we generated mice with genetic inactivation of the Acp1 locus and studied their response to long‐term pressure overload. Acp1−/− mice develop normally and ageing mice do not show pathology in major tissues under basal conditions. However, Acp1−/− mice are strikingly resistant to pressure overload hypertrophy and heart failure. Lmptp expression is high in the embryonic mouse heart, decreased in the postnatal stage, and increased in the adult mouse failing heart. We also show that LMPTP expression increases in end‐stage heart failure in humans. Consistent with their protected phenotype, Acp1−/− mice subjected to pressure overload hypertrophy have attenuated fibrosis and decreased expression of fibrotic genes. Transcriptional profiling and analysis of molecular signalling show that the resistance of Acp1−/− mice to pathological cardiac stress correlates with marginal re‐expression of fetal cardiac genes, increased insulin receptor beta phosphorylation, as well as PKA and ephrin receptor expression, and inactivation of the CaMKIIδ pathway. Our data show that ablation of Lmptp inhibits pathological cardiac remodelling and suggest that inhibition of LMPTP may be of therapeutic relevance for the treatment of human heart failure. © 2015 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Helping to drive the robustness of preclinical research – the assay capability tool
Authors: Gore Katrina , Stanley Phil 
Published: July 2015

AbstractNumerous articles in Nature, Science, Pharmacology Research and Perspectives, and other biomedical research journals over the past decade have highlighted that research is plagued by findings that are not reliable and cannot be reproduced. Poor experiments can occur, in part, as a consequence of inadequate statistical thinking in the experimental design, conduct and analysis. As it is not feasible for statisticians to be involved in every preclinical experiment many of the same journals have published guidelines on good statistical practice. Here, we outline a tool that addresses the root causes of irreproducibility in preclinical research in the pharmaceutical industry. The Assay Capability Tool uses 13 questions to guide scientists and statisticians during the development of in vitro and in vivo assays. It promotes the absolutely essential experimental design and analysis strategies and documents the strengths, weaknesses, and precision of an assay. However, what differentiates it from other proposed solutions is the emphasis on how the resulting data will be used. An assay can be assigned a low, medium, or high rating to indicate the level of confidence that can be afforded when making important decisions using data from that assay. This provides transparency on the appropriate interpretation of the assay's results in the light of its current capability. We suggest that following a well‐defined process during assay development and use such as that laid out within the Assay Capability Tool means that whatever the results, positive or negative, a researcher can have confidence to make decisions upon and publish their findings.
Key role of publication of clinical data for target validation
Authors: Hayes Ann 
Published: July 2015

AbstractDrug discovery productivity has failed to improve markedly in recent years and a key issue is high attrition due to efficacy failures in initial proof‐of concept clinical studies. This reflects the fact that preclinical “target validation” studies do not always translate into man, where ultimate target validation must reside. Given these facts, it is easy to see the importance of results from those first clinical validation studies for overall target validation. There are various initiatives to promote the publication of clinical data, but many clinical results, particularly negative results, remain unpublished, are published in obscure places or are published after a considerable delay. This gives rise to the potential that vast sums of money could be spent on compounds for which the molecular target has essentially been invalidated, but the data are not publicly available. Pharmacology, Research and Perspectives has indicated that it will welcome publication of all data pertinent to target validation, particularly negative data (clinical and preclinical), and it will do so in a form that should be relatively rapid and easy to achieve.
Replication – why we need to publish our findings
Authors: Curtis Michael J. , Abernethy Darrell R. 
Published: July 2015

AbstractThe pharmacology research sector is changing to accommodate a need for greater transparency and better standards. The themed articles contained herein explain how Pharmacology Research and Perspectives (PR&P) has responded to this agenda. This issue of PR&P contains three articles that consider the reliability of pharmacological research publications, and approaches to their improvement in this regard. This first article explains the importance of publishing findings that confirm or repudiate published findings (so called “replication” studies). It also emphasizes that PR&P actively encourages submission of such articles, and seeks to oppose the publication bias that favors publication of “positive” findings. The second paper explores some initiatives to publish “negative” clinical findings, including a PR&P initiative. The final paper elaborates a toolkit that can be applied to drug discovery research to facilitate the reliability of findings.
Revisiting the firm, industry, and country effects on profitability under recessionary and expansion periods: A multilevel analysis
Authors: Bamiatzi Vassiliki , Bozos Konstantinos , Cavusgil S. Tamer , Hult G. Tomas M. 
Published: July 2015

Research summary: Despite voluminous past research, the relevance of firm, industry, and country effects on profitability, particularly under adverse contexts, is still unclear. We reconcile institutional theory with the resource‐based view and industrial organization economics to investigate the effects of economic adversity, such as the 2008 global economic crisis. Using a three‐level random coefficient model, we examine 15,008 firms across 10 emerging and 10 developed countries for the 2005–2011 period. We find that firm effects become stronger under adversity, whereas industry effects become weaker, as well as country main and interaction effects, particularly among the emerging economies. These findings confirm our assumptions that the firm's own fate is, to a great extent, self‐determined; a reality that is even more pronounced during periods of extreme economic hardship.Managerial summary: In this research, we examine how generalized economic adversity affects the balance across the firm‐, industry‐, and country‐specific factors determining firm profitability. We specifically examine 15,008 firms from 10 emerging and 10 developed countries during the 2005–2011 period to investigate the effects of the 2008 global economic crisis on firm performance. We find that in such adverse conditions, the role of the industry and the country are reduced and the firm's own resources and capabilities become more pertinent for firm performance. This phenomenon is more pronounced across emerging markets. We conclude that the firm's own fate is, to a great extent, self‐determined, a reality that is markedly more evident during periods of extreme economic hardship. Copyright © 2015 John Wiley & Sons, Ltd.
Ephedra protects vascular endothelium cells from vinorelbine‐induced cytotoxicity by preserving endothelial nitric oxide synthase activity
Authors: Konaka Ken , Moriyama Kota , Okada Naoto , Nishisako Hirotaka , Shono Masayuki , Kawazoe Kazuyoshi , Ishizawa Keisuke 
Published: July 2015

ABSTRACTAimVinorelbine is an anticancer drug associated with vascular injury. The mechanism of vascular injury is associated with the decrease of endothelial nitric oxide synthase (eNOS), which regulates oxidative stress. Kakkonto, a traditional Japanese medicine, has anti‐inflammatory and anti‐oxidative effects. We evaluated the effect of kakkonto on vinorelbine‐induced vascular injury and its mechanism of action.MethodsHuman umbilical vein endothelial cells were used as the endothelial model. We compared vinorelbine‐induced cytotoxicity after pre‐incubation with the seven kakkonto components using ATP assay. Mitochondrial membrane potential was assessed using Mitochondrial Membrane Potential Assay Kit. Intracellular calcium ion concentration ([Ca2+]i) was measured with a calcium‐sensitive dye, Fluo‐4 AM. eNOS and Akt phosphorylation after ephedra extract or vinorelbine treatment were investigated on western blot.ResultsEphedra, a kakkonto component, protected cells against vinorelbine‐induced cytotoxicity. Ephedra extract preserved eNOS phosphorylation by increasing [Ca2+]i, but it had no effect on Akt phosphorylation. The increase in [Ca2+]i was mediated by Ca2+ influx via l‐type calcium channels. Additionally, inhibition of Ca2+ influx or eNOS phosphorylation abolished the effects of ephedra extract.ConclusionEphedra extract preserved eNOS phosphorylation following vinorelbine‐induced oxidative stress, thereby protecting cells from vinorelbine‐induced cytotoxicity. Moreover, the protective effect of ephedra extract is dependent on the increase of [Ca2+]i and the Ca2+/calmodulin‐dependent signal transduction pathway.
Habitat associations of breeding mallards and Canada geese in southern Ontario, Canada
Authors: Messmer David J. , Petrie Scott A. , Badzinski Shannon S. , Gloutney Mark L. , Schummer Michael L. 
Published: July 2015

ABSTRACTUnderstanding habitat associations of breeding mallards (Anas platyrhynchos) and Canada geese (Branta canadensis maxima) in the eastern US and Canada is important for conservation planning, yet studies at spatial scales useful to conservation planners have mostly occurred in the midcontinent prairie pothole region (PPR). Our broad objective was to determine whether breeding pairs were associated with similar habitat types in an eastern ecozone, the mixed woodland plain of southern Ontario, Canada, as they are in the PPR, despite substantial differences in relative habitat availability and land use practices. We used helicopter surveys and remote sensing to investigate habitat associations at landscape (25 km2) and local (500 m wetland buffer [79 ha]) scales during the 2008 and 2009 breeding seasons. At both spatial scales, mallard indicated breeding pairs (IBP) were positively associated with the abundance or area of temporary open water and emergent (seasonal or semipermanent) wetland types, similar to the PPR. However, against expectations, we did not detect an effect of grassland area. Canada goose IBP were most strongly associated with total wetland abundance, and not specifically with emergent and permanent open‐water wetlands as expected. At the local scale, goose IBP presence was positively associated with riverine wetland area. Unlike the PPR, our study area contained a high proportion of forested and riverine wetlands; however, with the exception of the riverine wetland–Canada goose association noted above, we did not detect a disproportionate influence of these wetland types on mallards or geese. © 2015 The Wildlife Society.
Natural Rumen‐Derived trans Fatty Acids Are Associated with Metabolic Markers of Cardiac Health
Authors: Da Silva Marine S. , Julien Pierre , Pérusse Louis , Vohl Marie‐Claude , Rudkowska Iwona 
Published: July 2015

AbstractEvidence suggests that industrial trans fatty acids (iTFA) impair lipid profiles while ruminant trans fatty acids (rTFA) may lower insulin resistance and blood pressure. The objective of this article was to determine if the plasma phospholipid percentage of rTFA is associated with a favorable cardiometabolic profile. We collected fasting blood samples from 200 individuals from Quebec city (QC, Canada) aged from 18 to 55 years old, including 100 obese (BMI ≥ 30 kg m−2) and 100 non‐obese (BMI < 30 kg m−2) men and women. Fatty acid levels in plasma phospholipids were determined using gas chromatography. After separating the subjects into two groups, according to the median percentage of rTFA in plasma phospholipids, participants in the group with higher percentages of rTFA (0.86 ± 0.24 %) had higher adiponectin levels (p = 0.01) and a lower blood pressure (systolic, p = 0.005; diastolic, p = 0.04). In contrast, concentrations in plasma phospholipids of elaidic acid, a major iTFA, are positively correlated with glycemia in non‐obese subjects (p = 0.01) and with both triacylglycerol (TAG) (p = 0.0007) and total cholesterol (TC) (p = 0.009) in obese subjects. These data suggest that rTFA may have beneficial effects on cardiometabolic risk factors conversely to their counterpart iTFA. Dietary sources of TFA should be taken into account in future cardiometabolic studies.
Effect of Agronomical Factors and Storage Conditions on the Tocopherol Content of Oblica and Leccino Virgin Olive Oils
Authors: Jukić Špika Maja , Kraljić Klara , Koprivnjak Olivera , Škevin Dubravka , Žanetić Mirella , Katalinić Miro 
Published: July 2015

AbstractThe influence of agronomical factors (two growing areas and four harvest periods) and storage conditions of virgin olive oils (room temperature, +4 and −20 °C) on tocopherols was investigated on two cultivars having significantly different tocopherol content (Oblica 269–443 mg/kg, Leccino 403–784 mg/kg). α‐Tocopherol accounted for 97 % of total tocopherols and its content decreased during ripening of both cultivars. In a warmer growing area both cultivars gained a higher γ‐tocopherol content while only Leccino showed a higher content of α‐tocopherol. After 12 months of storage α‐tocopherol content decreased by up to 27 %. Lower storage temperatures did not always contribute to the higher stability of α‐tocopherol compared to room temperature.