bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resveratrol prevents cadmium activation of Erk1/2 and JNK pathways from neuronal cell death via protein phosphatases 2A and 5
Authors: Liu Chunxiao , Zhang Ruijie , Sun Chenxia , Zhang Hai , Xu Chong , Liu Wen , Gao Wei , Huang Shile , Chen Long 
Published: July 2015

AbstractCadmium (Cd), a toxic environmental contaminant, induces neurodegenerative disorders. Resveratrol, a natural product, has been found to exert neuroprotective effects. However, little is known regarding the effect of resveratrol on Cd‐evoked neurotoxicity. Here, we show that resveratrol effectively reversed Cd‐elicited cell viability reduction, morphological change, nuclear fragmentation and condensation, as well as activation of caspase‐3 in neuronal cells, implying neuroprotection against Cd‐poisoning by resveratrol. Further research revealed that both c‐Jun N‐terminal kinase (JNK) and extracellular signal‐regulated kinases 1/2 (Erk1/2) were involved in the inhibitory effect of resveratrol on Cd‐induced cell death, as selective inhibitors of Erk1/2 (U0126) and JNK (SP600125), or over‐expression of dominant negative mitogen‐activated protein kinase kinase 1 (MKK1) or dominant negative c‐Jun potentiated resveratrol's prevention of Cd‐induced phosphorylation of JNK and Erk1/2, as well as cell death in neuronal cells. Interestingly, resveratrol potently rescued the cells from Cd‐induced suppression of protein phosphatases 2A (PP2A) and 5 (PP5) activity. Over‐expression of PP2A or PP5 strengthened the inhibitory effects of resveratrol on Cd‐induced activation of Erk1/2 and/or JNK, as well as cell death. The results indicate that resveratrol prevents Cd‐induced activation of Erk1/2 and JNK pathways and neuronal cell death in part via activating PP2A and PP5. Our findings strongly support the notion that resveratrol may serve as a potential therapeutic agent in the prevention of Cd‐induced neurodegenerative diseases.
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Resveratrol, a natural polyphenol compound, has been found to exert neuroprotective effects. This study uncovers that resveratrol prevents cadmium (Cd)‐induced activation of Erk1/2 and JNK pathways and neuronal cell death via activating PP2A and PP5. The findings propose that resveratrol may serve as a potential therapeutic agent in the prevention of Cd‐induced neurodegenerative diseases.
Deficits in behavioral sensitization and dopaminergic responses to methamphetamine in adenylyl cyclase 1/8‐deficient mice
Authors: Bosse Kelly E. , Charlton Jennifer L. , Susick Laura L. , Newman Brooke , Eagle Andrew L. , Mathews Tiffany A. , Perrine Shane A. , Conti Alana C. 
Published: July 2015

AbstractThe cAMP/protein kinase A pathway regulates methamphetamine (METH)‐induced neuroplasticity underlying behavioral sensitization. We hypothesize that adenylyl cyclases (AC) 1/8 mediate these neuroplastic events and associated striatal dopamine regulation. Locomotor responses to METH (1 and 5 mg/kg) and striatal dopamine function were evaluated in mice lacking AC 1/8 (DKO) and wild‐type (WT) mice. Only 5 mg/kg METH induced an acute locomotor response in DKO mice, which was significantly attenuated versus WT controls. DKO mice showed a marked attenuation in the development and expression of METH‐induced behavioral sensitization across doses relative to WT controls. While basal and acute METH (5 mg/kg)‐evoked accumbal dialysate dopamine levels were similar between genotypes, saline‐treated DKO mice showed elevated tissue content of dopamine and homovanillic acid in the dorsal striatum (DS), reflecting dysregulated dopamine homeostasis and/or metabolism. Significant reductions in DS dopamine levels were observed in METH‐sensitized DKO mice compared to saline‐treated controls, an effect not observed in WT mice. Notably, saline‐treated DKO mice had significantly increased phosphorylated Dopamine‐ and cAMP‐regulated phosphoprotein levels, which were not further augmented following METH sensitization, as observed in WT mice. These data indicate that AC 1/8 are critical to mechanisms subserving drug‐induced behavioral sensitization and mediate nigrostriatal pathway METH sensitivity.
imageCalcium/calmodulin‐stimulated adenylyl cyclase (AC) isoforms 1 and 8 were studied for their involvement in the adaptive neurobehavioral responses to methamphetamine. AC 1/8 double knockout (DKO) mice showed heightened basal locomotor activity and dorsal striatal dopamine responsivity. Conversely, methamphetamine‐induced locomotor activity was attenuated in DKO mice, accompanied by reductions in dopamine and HVA content and impaired DARPP‐32 activation. These findings indicate AC 1/8 signaling regulates the sensitivity of the nigrostriatal pathway subserving stimulant and neuroadaptive sensitizing effects of methamphetamine. 3‐MT, 3‐methoxytyramine; Ca2+, calcium; CaM, calmodulin; cdk5; cyclin‐dependent kinase 5; DA, dopamine; DARPP‐32, dopamine‐ and cAMP‐regulated phosphoprotein; D1R, dopamine D1 receptor; HVA, homovanillic acid; PKA, protein kinase A.
Changes in the sebaceous gland in patients with male pattern hair loss (androgenic alopecia)
Authors: Kure Katsuhiro , Isago Tsukasa , Hirayama Takeshi 
Published: July 2015

SummaryBackgroundThe sebaceous gland and the follicular bulge region have important role in biology of the hair. They initiate destruction of the hair follicle both in human and animal models in certain conditions. The morphometric feature of the sebaceous gland is not well understood so as the distribution of the bulge stem cells in pathological conditions of male pattern hair loss or androgenic alopecia (AGA).ObjectivesThe authors perform morphometric analysis of the sebaceous gland in AGA patients and also study distribution of the follicular stem cells in the bulge region in these populations.MethodsTwo hundred and fifty cases of glass slide specimen from Japanese patients with male pattern hair loss were reviewed. Among these, 23 cases of the longitudinal (vertical) sections of the scalp skin with diagnosis of AGA were found and analyzed for the morphometric characteristics. Each sebaceous gland area was measured using NIH imagej system and statistically analyzed. For the identification of the follicular bulge region, an immunohistochemistry using anticytokeratin 15 (C8/144B clone) was carried out in the cases of AGA.ResultsThe sebaceous gland area of the AGA group was noticeably increased, while the size of each sebaceous gland remains unchanged. It has more lobules in the hair follicular unit in the AGA population. In the immunohistochemistry, the follicular stem cells are present in the bulge regions in cases of AGA.ConclusionsThe overgrowth (multilobulation) of the sebaceous gland and relative preservation of the follicular stem cells suggest that the changes in the sebaceous gland could be an important factor in the pathology of AGA.
Regulatory approval and a first‐in‐human phase I clinical trial of a monoclonal antibody produced in transgenic tobacco plants
Authors: Ma Julian K‐C. , Drossard Jürgen , Lewis David , Altmann Friedrich , Boyle Julia , Christou Paul , Cole Tom , Dale Philip , van Dolleweerd Craig J. , Isitt Valerie , Katinger Dietmar , Lobedan Martin , Mertens Hubert , Paul Mathew J. , Rademacher Thomas , Sack Markus , Hundleby Penelope A. C. , Stiegler Gabriela , Stoger Eva , Twyman Richard M. , Vcelar Brigitta , Fischer Rainer 
Published: July 2015

SummaryAlthough plant biotechnology has been widely investigated for the production of clinical‐grade monoclonal antibodies, no antibody products derived from transgenic plants have yet been approved by pharmaceutical regulators for clinical testing. In the Pharma‐Planta project, the HIV‐neutralizing human monoclonal antibody 2G12 was expressed in transgenic tobacco (Nicotiana tabacum). The scientific, technical and regulatory demands of good manufacturing practice (GMP) were addressed by comprehensive molecular characterization of the transgene locus, confirmation of genetic and phenotypic stability over several generations of transgenic plants, and by establishing standard operating procedures for the creation of a master seed bank, plant cultivation, harvest, initial processing, downstream processing and purification. The project developed specifications for the plant‐derived antibody (P2G12) as an active pharmaceutical ingredient (API) based on (i) the guidelines for the manufacture of monoclonal antibodies in cell culture systems; (ii) the draft European Medicines Agency Points to Consider document on quality requirements for APIs produced in transgenic plants; and (iii) de novo guidelines developed with European national regulators. From the resulting process, a GMP manufacturing authorization was issued by the competent authority in Germany for transgenic plant‐derived monoclonal antibodies for use in a phase I clinical evaluation. Following preclinical evaluation and ethical approval, a clinical trial application was accepted by the UK national pharmaceutical regulator. A first‐in‐human, double‐blind, placebo‐controlled, randomized, dose‐escalation phase I safety study of a single vaginal administration of P2G12 was carried out in healthy female subjects. The successful completion of the clinical trial marks a significant milestone in the commercial development of plant‐derived pharmaceutical proteins.
Commercialization of new biotechnology: a systematic review of 16 commercial case studies in a novel manufacturing sector
Authors: Paul Matthew J. , Thangaraj Harry , Ma Julian K.‐C. 
Published: July 2015

SummaryThe 1980s and 1990s saw a major expansion of biotechnology into new areas of science including genomics and recombinant technologies. This was coupled to the widespread emergence of academics into the commercial sector as they were encouraged to spin out companies or commercialize their intellectual property. There were many opportunities to raise investment, and extraordinary success stories were prominent across many areas of technology. The field of plant biotechnology for manufacturing recombinant pharmaceuticals (molecular pharming) emerged and was developed in this period. Like other biotechnologies, this was an exciting new development which offered some very obvious benefits and commercial advantages. In particularly, plant molecular pharming represented a highly novel and potentially disruptive manufacturing technology for recombinant proteins. Twenty‐five years on, a series of interviews with senior members of sixteen of the most prominent companies involved in the field provides insight into the original drivers for commercialization, strategic thinking and planning behind key commercial decisions and an insider view into the major reasons for commercial success or failure. These observations and recurring themes identified across a number of commercial ventures remain relevant today, as new biotech companies continue to spin out of the world of academia.
ASG2 is a farnesylated DWD protein that acts as ABA negative regulator in Arabidopsis
Authors: Dutilleul Christelle , Ribeiro Iliana , Blanc Nathalie , Nezames Cynthia D. , Deng Xing Wang , Zglobicki Piotr , Palacio Barrera Ana María , Atehortùa Lucia , Courtois Martine , Labas Valérie , Giglioli‐Guivarc'h Nathalie , Ducos Eric 
Published: July 2015

AbstractThe tagging‐via‐substrate approach designed for the capture of mammal prenylated proteins was adapted to Arabidopsis cell culture. In this way, proteins are in vivo tagged with an azide‐modified farnesyl moiety and captured thanks to biotin alkyne Click‐iT® chemistry with further streptavidin‐affinity chromatography. Mass spectrometry analyses identified four small GTPases and ASG2 (ALTERED SEED GERMINATION 2), a protein previously associated to the seed germination gene network. ASG2 is a conserved protein in plants and displays a unique feature that associates WD40 domains and tetratricopeptide repeats. Additionally, we show that ASG2 has a C‐terminal CaaX‐box that is farnesylated in vitro. Protoplast transfections using CaaX prenyltransferase mutants show that farnesylation provokes ASG2 nucleus exclusion. Moreover, ASG2 interacts with DDB1 (DAMAGE DNA BINDING protein 1), and the subcellular localization of this complex depends on ASG2 farnesylation status. Finally, germination and root elongation experiments reveal that asg2 and the farnesyltransferase mutant era1 (ENHANCED RESPONSE TO ABSCISIC ACID (ABA) 1) behave in similar manners when exposed to ABA or salt stress. To our knowledge, ASG2 is the first farnesylated DWD (DDB1 binding WD40) protein related to ABA response in Arabidopsis that may be linked to era1 phenotypes.
Photoreceptors in Chemotrophic Prokaryotes: The Case of Acinetobacter spp. Revisited
Authors: Nudel Clara B. , Hellingwerf Klaas J. 
Published: July 2015

AbstractA comprehensive description of blue light using flavin (BLUF) photosensory proteins, including preferred domain architectures and the molecular mechanism of their light activation and signal generation, among chemotrophic prokaryotes is presented. Light‐regulated physiological responses in Acinetobacter spp. from environmental and clinically relevant strains are discussed. The twitching motility response in A. baylyi sp. ADP1 and the joint involvement of three of the four putative BLUF‐domain‐containing proteins in this response, in this species, is presented as an example of remarkable photoreceptor redundancy.
International Intercomparison of Solar UVR Spectral Measurement Systems in Melbourne in 2013
Authors: Gies Peter , Hooke Rebecca , McKenzie Richard , O'Hagan John , Henderson Stuart , Pearson Andy , Khazova Marina , Javorniczky John , King Kerryn , Tully Matt , Kotkamp Michael , Forgan Bruce , Rhodes Stephen 
Published: July 2015

AbstractMonitoring ambient solar UVR levels provides information on how much there is in both real time and historically. Quality assurance of ambient measurements of solar UVR is critical to ensuring accuracy and stability and this can be achieved by regular intercomparisons of spectral measurement systems with those of other organizations. In October and November of 2013 a solar UVR spectroradiometer from Public Health England (PHE) was brought to Melbourne for a campaign of intercomparisons with a new Bentham spectrometer of Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) and one at the Australian Bureau of Meteorology (BOM), supported by New Zealand's National Institute for Water and Atmosphere (NIWA). Given all three spectroradiometers have calibrations that are traceable to various national standards, the intercomparison provides a chance to determine measurement uncertainties and traceability that support UV measurement networks in Australia, New Zealand and the UK. UV Index measurements from all three systems were compared and ratios determined for clear sky conditions when the scans from each instrument were within 2 min of each other. While wavelengths below 305 nm showed substantial differences between the PHE unit and the two other systems, overall the intercomparison results were encouraging, with mean differences in measured UV Index between the BOM/NIWA and those of PHE and ARPANSA of <0.1% and 7.5%, respectively.
Taxing Fracking: The Politics of State Severance Taxes in the Shale Era
Authors: Rabe Barry G. , Hampton Rachel L. 
Published: July 2015

AbstractStates producing gas and oil have long levied severance taxes at the point of extraction, commonly placing most revenues into general funds. These taxes have assumed new meaning in many states amid the expansion of gas and oil production accompanying the advent of hydraulic fracturing. We reviewed all major statutes and constitutional amendments related to severance taxes that were enacted at the state level during the first decade of the “shale era” (2005–14). There have been only modest adjustments in statutory tax rates and some evidence that states have attempted to reduce these rates, possibly in response to growing national production. In turn, there is also evidence that states have begun to pursue more targeted strategies for revenue use, including some expanded focus on responding to the negative externalities linked to drilling, expanded revenue sharing with localities, and increased long‐term protection of resources through state trust funds.
Focusing Events and Changes in Ecologies of Policy Games: Evidence from the Paraná River Delta
Authors: Berardo Ramiro , Olivier Tomás , Lavers Anthony 
Published: July 2015

AbstractSolving environmental problems on a regional scale demands joint efforts by multiple stakeholders, but coordinating such efforts can be difficult in complex governance systems. In this article, we combine the literature in Adaptive Governance with the Ecology of Policy Games (EPGs) framework to enhance our understanding of how complex governance systems react to environmental focusing events. We study the EPGs in the Paraná River delta in Argentina following widespread fires caused by slash‐and‐burn practices in 2008, and analyze how new forums created to address the consequences of this event differ from the forums created prior to the event in terms of their capacity to attract stakeholders and to provide higher interconnectivity to the whole governance system. Furthermore, we offer an initial evaluation of the Comprehensive Strategic Plan for the Conservation and Sustainability of the Paraná River delta, the main forum in the EPGs created to address the negative consequences of the focusing event. Finally, we discuss the implications of our findings for the study of complex governance systems where stakeholders are able to address the management of natural resources at a regional scale.
Risk Analysis of Nanomaterials: Exposing Nanotechnology's Naked Emperor
Authors: Miller Georgia , Wickson Fern 
Published: July 2015

AbstractRisk analysis (encompassing risk assessment, management, and communication) is touted internationally as the most appropriate approach for governing nanomaterials. In this article, we survey existing criticisms of risk assessment as a basis for regulatory decision making on emerging technologies, particularly highlighting its exclusion of key societal dimensions, its epistemological underdetermination, and its lack of democratic accountability. We then review the specific case of nanomaterials and identify six major barriers to the effective operation of both risk assessment and risk management. These include a lack of: nano‐specific regulatory requirements, shared definitions, validated and accessible methods for safety testing, available scientific knowledge, reliable information on commercial use, and capacity for exposure mitigation. Finding the knowledge, standards, methods, tools, definitions, capacity, and political commitment all insufficient, we argue that risk analysis is a “naked emperor” for nanomaterial governance. We therefore suggest that additional concepts and approaches are essential for nanomaterials policy and regulation.
Political Competition, Agenda Power, and Incentives to Innovate: An Empirical Examination of Vested‐Interest Theory
Authors: Balalaeva Dina 
Published: July 2015

AbstractTechnological innovations are by no means Pareto‐improving. I build on the argument that incumbent innovators can use political means to block rival innovations by emphasizing that the competitiveness of political system and some political institutions may diminish their ability to do so. I specify an institutional mechanism of agenda power, which provides newcomers with an improved ability to enter the game. The number of agenda power holders varies significantly among political systems, electoral systems, and administrative structures. With a sample of about 100 countries and across 20 years I show that politically competitive regimes, majoritarian electoral rules, and federal structures supply more holders of agenda power in comparison to their counterparts and, other things being equal, produce more innovations.
Cultural Policy and Governance: Reviewing Policies Related to Cultural and Creative Industries Implemented by the Central Government of Taiwan Between 2002 and 2012
Authors: Lee Chang Bin 
Published: July 2015

AbstractCultural and creative industries have exhibited rapid changes in recent years, and public sectors worldwide have expanded interest in policies related to these industries as a means of promoting culture, innovation, and economic vitality. This article argues that the cultural values promoted by and economic significance of cultural and creative sectors are essential to the formation of policy and to the development of new industries. This article offers insight into cultural policy that has governed regional and local development, and addresses academic debates about policy related to cultural and creative industries based on several cultural, economic, and geographical factors. In addition, this article presents the results of analyzing various theories and case studies, based on how the Central Government of Taiwan (CGT) has adopted policies to promote cultural and creative industries. The research results link areas of cultural and economic development with policies enacted by the CGT. Ideas concerning the cultural ministry, industrial development, civic boosterism, subsidies, regional development, creative clusters, tourists and tourism businesses, and export markets are areas of emphasis in this study.
Truncated Linear Models for Functional Data
Authors: Hall Peter , Hooker Giles 
Published: July 2015

Summary
A conventional linear model for functional data involves expressing a response variable Y in terms of the explanatory function X (t), via the model Y=a+∫Ib(t)X(t)dt+error, where a is a scalar, b is an unknown function and I=[0,α] is a compact interval. However, in some problems the support of b or X, I1 say, is a proper and unknown subset of I, and is a quantity of particular practical interest. Motivated by a real data example involving particulate emissions, we develop methods for estimating I1. We give particular emphasis to the case I1=[0,θ], where θ ∈ (0, α], and suggest two methods for estimating a, b and θ jointly; we introduce techniques for selecting tuning parameters; and we explore properties of our methodology by using both simulation and the real data example mentioned above. Additionally, we derive theoretical properties of the methodology and discuss implications of the theory. Our theoretical arguments give particular emphasis to the problem of identifiability.
Anaphylactic Shock at the End of Hemodialysis
Authors: Aziz Nivin , Luna Carla , Mirza Farheen , Tobin Mary 
Published: July 2015

AbstractAllergic reactions to epoetin alfa, including anaphylaxis, have been described but desensitization in the setting of an IgE‐mediated reaction has not been reported. We present a case of a hemodialysis patient who developed symptoms of an IgE‐mediated allergic response to epoetin alfa that occurred after each administration. These reactions progressed to a single episode of anaphylaxis with generalized pruritus, urticaria, oropharyngeal edema, and hypotension that prompted its discontinuation. Intradermal skin testing confirmed an allergic response to this agent. The patient then underwent a desensitization procedure to epoetin alpha after which she was able to tolerate it without further problems.
Movement and deletion after syntax: Licensing by inflection reconsidered
Authors: Saab Andrés , Lipták Anikó 
Published: July 2015

AbstractIn this paper we study the interaction between ellipsis and inflectional morphology and put forward a generalization about ellipsis blocking the application of some morphological operations. Working in the Distributed Morphology framework, we will demonstrate this generalization in the realm ofNPellipsis. We will show thatNPellipsis can lead to stranded affix filter violations, and that there are various strategies languages can resort to in order to resolve problems of convergence that stranded affixes cause at thePFinterface. The resolution of the stranded affix filter configuration is responsible for the well‐known observation that heads precedingNPellipsis sites need to show overt inflection in languages that inflect these heads (Lobeck 1995).