bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding cell death in parkinson's disease
Authors: Jenner Peter , C. Warren Olanow  
Published: February 2014

AbstractCurrent concepts of the cause of Parkinson's disease (PD) suggest a role for both genetic and environmental influences. Common to a variety of potential causes of nigral cell degeneration in PD is the involvement of oxidative stress. Postmortem analysis shows increased levels of iron, decreased complex I activity, and a decrease in reduced glutathione (GSH) levels. The decrease in GSH levels may be a particularly important component of the cascade of events leading to cell death because it occurs in the presymptomatic stage of PD and may directly induce nigral cell degeneration or render neurons susceptible to the actions of toxins. There is evidence suggesting that oxidative stress might originate in glial cells rather than in neurons, and alterations in glial function may be an important contributor to the pathologic process that occurs in PD. Oxidative damage occurs in the brain in PD, as shown by increased lipid peroxidation and DNA damage in the substantia nigra. Increased protein oxidation is also apparent, but this occurs in many areas of the brain and raises the specter of a more widespread pathologic process occurring in PD to which the substantia nigra is particularly vulnerable. The inability of the substantia nigra to handle damaged or mutant (eg, α‐synuclein) proteins may lead to their aggregation and deposition and to the formation of Lewy bodies. Indeed, Lewy bodies stain for both α‐synuclein and nitrated proteins. Current evidence enables us to hypothesize that a failure to process structurally modified proteins in regions of the brain exhibiting oxidative stress is a cause of both familial and sporadic PD.
Mitochondria in the etiology and pathogenesis of parkinson's disease
Authors: Schapira A. H. V. , Gu M. , Taanman J.‐W. , Tabrizi S. J. , Seaton T. , Cleeter M. , Cooper J. M. 
Published: February 2014

AbstractMitochondria play a critical role in cellular energy metabolism. The identification of a respiratory chain defect in Parkinson's disease (PD) provides not only a direct link with toxin models of parkinsonism but also insight into the mechanisms involved in etiology and pathogenesis. The presence of the complex I deficiency in PD substantia nigra and platelets suggests the involvement of a systemic cause. Genomic transplantation studies have been undertaken that involve the transfer to a novel nuclear background of mitochondrial DNA (mtDNA) from PD patients with a complex I defect, followed by both mixed and clonal expansion of the resulting cybrids. The mixed cybrids with the PD mtDNA expressed the complex I defect present in the original PD donor platelets. Clonal expansion of one such mixed cybrid culture produced a spectrum of clones with complex I and complex IV activities, ranging from severe deficiency to normal range, a pattern typical of a heteroplasmic mtDNA mutation. Histochemical, immunohistochemical, and functional assessments of ΔψM all showed a pattern in the PD clones typical of that produced by a mtDNA mutation. Patients with focal dystonia and a platelet complex I defect were used as disease controls for the cybrid studies. The mitochondrial abnormality was eradicated by transfer of dystonia mtDNA to a control nuclear background in both mixed and clonal cybrids, with no evidence of clonal heterogeneity. These results help to validate our findings in the PD patients and suggest that the complex I deficiency in dystonia is not due to an abnormality of mtDNA. We hypothesize that the mtDNA defect alone may be the cause of PD in a proportion of patients and may contribute to pathogenesis in others. Identification of the mtDNA genotype responsible for PD may allow the testing of neuroprotective strategies in appropriate patients.
Mitochondrial dysfunction in parkinson's disease
Authors: Mizuno Yoshikuni , Yoshino Hiroyo , Ikebe Shin‐Ichiro , Hattori Nobutaka , Kobayashi Tomonori , Shimoda‐Matsubayashi Satoe , Matsumine Hiroto , Kondo Tomoyoshi 
Published: February 2014

AbstractThis review discusses the etiology and pathogenesis of Parkinson's disease (PD). Mitochondrial respiratory failure and oxidative stress appear to be two major contributors to nigral neuronal death in PD. Complex I deficiency has been reported by several groups and appears to be one of the basic abnormalities responsible for mitochondrial failure. The principal question is whether or not complex I deficiency is primary or secondary. The second question is whether or not complex I deficiency is localized in the nigrostriatal system or is systemically present. It is our impression that complex I deficiency is not the primary cause but that its deficiency appears to be systemic. The primary cause may be the combination of genetic background and potential nigral neurotoxins. Exposure of nigral neurons to a high risk for oxidative damage because of its high dopamine content may be the reason for more pronounced nigral complex I deficiency compared to systemic organs. Oxidative stress and mitochondrial failure produce a vicious cycle in nigral neurons. To explore the genetic risk factors of sporadic PD, studies on familial PD and parkinsonism are important. Recently, an autosomal dominant form of familial PD was found to be caused by point mutations of the α‐synuclein gene, and an autosomal recessive familial parkinsonism was mapped to the long arm of chromosome 6 near the Mn‐SOD gene locus. Information obtained in these familial cases will contribute to the research on sporadic PD.
Excitotoxicity and nitric oxide in parkinson's disease pathogenesis
Authors: M. Flint Beal  
Published: February 2014

AbstractA potential role for excitotoxic processes in Parkinson's disease (PD) has been strengthened by the recent observations that there appears to be a mitochondrially encoded defect in complex I activity of the electron transport chain. An impairment of oxidative phosphorylation will enhance vulnerability to excitotoxicity. Substantia nigra neurons possess N‐methyl‐D‐aspartate receptors and there are glutamatergic inputs into the substantia nigra from both the cerebral cortex and the subthalamic nucleus. After activation of excitatory amino acid receptors, there is an influx of calcium followed by activation of neuronal nitric oxide (NO) synthase, which can then lead to the generation of peroxynitrite. Consistent with such a mechanism, studies of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine neurotoxicity in both mice and primates have shown that inhibition of neuronal NO synthase exerts neuroprotective effects. Studies utilizing excitatory amino acid receptor antagonists have been inconsistent in mice but show significant neuroprotective effects in primates. These results raise the prospect that excitatory amino acid antagonists for neuronal NO synthase inhibitors might be useful in the treatment of PD.
Neuroprotective and neurorestorative properties of GDNF
Authors: Gash Don M. , Zhang Zhiming , Gerhardt Greg 
Published: February 2014

AbstractGlial cell line‐derived neurotrophic factor (GDNF) promotes recovery of the injured nigrostriatal dopamine system and improves motor functions in both rodent and nonhuman primate models of Parkinson's disease (PD). The neurorestorative effects of a single administration of GDNF last for at least 1 month and can be maintained in rhesus monkeys by monthly injections. Adult midbrain dopamine neurons stimulated by GDNF show increased cell size, neurite extent, and expression of phenotypic markers. In parkinsonian nonhuman primates, GDNF treatment improves three of the cardinal features of PD: bradykinesia, rigidity, and postural instability. Although intracerebral administration is necessary because of the blood‐brain barrier, intraventricular, intrastriatal, and intranigral routes of administration have been found to be efficacious in rodents and nonhuman primates. GDNF also induces neuroprotective changes in dopamine neurons which are active within hours after trophic factor administration. The powerful neuroprotective and neurorestorative properties of GDNF seen in preclinical studies suggest that trophic factors may play an important role in treating PD.
Neuroprotection for parkinson's disease
Authors: Koller William C. 
Published: February 2014

AbstractLevodopa is the most effective drug available for the treatment of Parkinson's disease (PD). As a precursor of dopamine, levodopa causes an increase in brain dopamine, which is depleted in PD. However, long‐term levodopa therapy is associated with complications such as dyskinesias, motor fluctuations, and mental status changes. The treatment of these side effects is a major challenge for the clinician.
The causes of parkinson's disease are being unraveled and rational neuroprotective therapy is close to reality
Authors: Marsden C. David , Olanow C. Warren 
Published: February 2014

AbstractThere has been significant progress in our knowledge of the cause, the pathogenesis, and the nature of the mechanism of cell death in Parkinson's disease (PD). Mutations in single genes have now been shown to be able to cause PD but likely only account for a small number of cases. Alternatively, there is evidence that environmental factors play a large role in the majority of cases of sporadic PD. Most likely, genetic factors predispose patients to develop PD if combined with other gene mutations or environmental toxins. Interest has thus focused on factors that contribute to the pathogenesis of neurodegeneration and the mechanism of cell death in an attempt to design a neuroprotective therapy. Oxidant stress, mitochondrial dysfunction, excitotoxicity with excess nitric oxide formation, and glia and inflammatory processes are all thought to contribute to the cell death process and agents that interfere with these events may be neuroprotective. It is now generally held that the final culmination of these events is the induction of apoptosis in nigral dopaminergic neurons and this too offers opportunities for providing neuroprotection. A rational argument can be made for investigating a large number of different approaches or combination of approaches in the hope of developing a meaningful neuroprotective therapy, using clinically relevant indices and neuroimaging markers of nigral dopaminergic neurons. It is evident that conventional approaches to trials that utilize large numbers of patients in search of small incremental effects are costly and time consuming. As such, it will be virtually impossible to test all of the potentially valuable neuroprotective agents that are now at hand, let alone those that will likely soon emerge. We suggest that it may be more profitable to test a large number of agents in a small number of selected patients in search of a more robust neuroprotective effect. In this way, we will reduce the risk of missing a powerful neuroprotective treatment with a treatment that might not otherwise have been studied because of a lack of time, money, or patients.
Assessing Chemical Heterogeneity at the Nanoscale in Mixed‐Ligand Metal–Organic Frameworks with the PTIR Technique
Authors: Katzenmeyer Aaron M. , Canivet Jerome , Holland Glenn , Farrusseng David , Centrone Andrea 
Published: February 2014

AbstractRecently, the use of mixtures of organic‐building‐block linkers has given chemists an additional degree of freedom for engineering metal–organic frameworks (MOFs) with specific properties; however, the poor characterization of the chemical complexity of such MixMOF structures by conventional techniques hinders the verification of rational design. Herein, we describe the application of a technique known as photothermal induced resonance to individual MixMOF microcrystals to elucidate their chemical composition with nanoscale resolution. Results show that MixMOFs isoreticular to In‐MIL‐68, obtained either directly from solution or by postsynthetic linker exchange, are homogeneous down to approximately 100 nm. Additionally, we report a novel in situ process that enables the engineering of anisotropic domains in MOF crystals with submicron linker‐concentration gradients.
The Formazanate Ligand as an Electron Reservoir: Bis(Formazanate) Zinc Complexes Isolated in Three Redox States
Authors: Chang Mu‐Chieh , Dann Thomas , Day David P. , Lutz Martin , Wildgoose Gregory G. , Otten Edwin 
Published: February 2014

AbstractThe synthesis of bis(formazanate) zinc complexes is described. These complexes have well‐behaved redox‐chemistry, with the ligands functioning as a reversible electron reservoir. This allows the synthesis of bis(formazanate) zinc compounds in three redox states in which the formazanate ligands are reduced to “metallaverdazyl” radicals. The stability of these ligand‐based radicals is a result of the delocalization of the unpaired electron over four nitrogen atoms in the ligand backbone. The neutral, anionic, and dianionic compounds (L2Zn0/−1/−2) were fully characterized by single‐crystal X‐ray crystallography, spectroscopic methods, and DFT calculations. In these complexes, the structural features of the formazanate ligands are very similar to well‐known β‐diketiminates, but the nitrogen‐rich (NNCNN) backbone of formazanates opens the door to redox‐chemistry that is otherwise not easily accessible.
Coordination Complexes of Ph3Sb2+ and Ph3Bi2+: Beyond Pnictonium Cations
Authors: Robertson Alasdair P. M. , Burford Neil , McDonald Robert , Ferguson Michael J. 
Published: February 2014

AbstractThe syntheses of salts containing ligand‐stabilized Ph3Sb2+ and Ph3Bi2+ dications have been realized by in situ formation of Ph3Pn(OTf)2 (Pn=Sb or Bi) and subsequent reaction with OPPh3, dmap and bipy. The solid‐state structures demonstrate diversity imposed by the steric demands and nature of the ligands. The synthetic method has the potential for broad application enabling widespread development of the coordination chemistry for PnV acceptors.
Aerobic Oxidation in Nanomicelles of Aryl Alkynes, in Water at Room Temperature
Authors: Handa Sachin , Fennewald James C. , Lipshutz Bruce H. 
Published: February 2014

AbstractOn the basis of the far higher solubility of oxygen gas inside the hydrocarbon core of nanomicelles, metal and peroxide free aerobic oxidation of aryl alkynes to β‐ketosulfones has been achieved in water at room temperature. Many examples are offered that illustrate broad functional group tolerance. The overall process is environmentally friendly, documented by the associated low E Factors.
9‐Membered Carbocycle Formation: Development of Distinct Friedel–Crafts Cyclizations and Application to a Scalable Total Synthesis of (±)‐Caraphenol A
Authors: Wright Nathan E. , Snyder Scott A. 
Published: February 2014

AbstractExplorations into a series of different approaches for 9‐membered carbocycle formation have afforded the first reported example of a 9‐exo‐dig ring closure via a AuIII‐promoted reaction between an alkyne and an aryl ring as well as several additional, unique Friedel–Crafts‐type cyclizations. Analyses of the factors leading to the success of these transformations are provided, with the application of one of the developed 9‐membered ring closures affording an efficient and scalable synthesis of the bioactive resveratrol trimer caraphenol A. That synthesis proceeded with an average yield of 89 % per step (7.8 % overall yield) and has provided access to more than 600 mg of the target molecule.
Deracemisierung durch simultane bio‐oxidative Racematspaltung und Stereoinversion
Authors: Schrittwieser Joerg H. , Groenendaal Bas , Resch Verena , Ghislieri Diego , Wallner Silvia , Fischereder Eva‐Maria , Fuchs Elisabeth , Grischek Barbara , Sattler Johann H. , Macheroux Peter , Turner Nicholas J. , Kroutil Wolfgang 
Published: February 2014

AbstractDeracemisierung, also die Umwandlung eines Racemats in ein enantiomerenreines Produkt mit theoretisch 100 % Ausbeute und 100 % ee, stellt eine attraktive, aber auch anspruchsvolle Option für die asymmetrische Synthese dar. Hier beschreiben wir ein neuartiges Konzept einer chemo‐enzymatischen Deracemisierung mittels einer Kaskadenreaktion. Die Reaktionsfolge beinhaltet zwei enantioselektive Oxidationsschritte und einen nicht stereoselektiven Reduktionsschritt, durch welche zur gleichen Zeit eine Stereoinversion und eine kinetische Racematspaltung realisiert werden. Dieses Konzept wird anhand der Umwandlung von rac‐Benzylisochinolinen in optisch reine (S)‐Berbine vorgestellt. Die racemischen Substrate wurden in enantiomerenreine Produkte (ee>97 %) umgewandelt, wobei Umsätze von bis zu 98 % und Ausbeuten von bis zu 88 % erreicht wurden.
Geometric Requirements for Hydrocarbon Catalytic Sites on Platinum Surfaces
Authors: Gao Jie , Zhao Haibo , Yang Xiaofang , Koel Bruce E. , Podkolzin Simon G. 
Published: February 2014

AbstractVibrational spectroscopic measurements and density functional calculations were used to identify a preferential catalytic mechanism for the transformation of acetylene, HCCH, to vinylidene, CCH2, on surfaces of Pt‐Sn ordered alloys. In this mechanism, two adjacent Pt atoms adsorb an acetylene molecule and a third neighboring Pt atom is required for stabilizing the reacting H atom during the transformation. Therefore, unlike a direct H shift along the CC bond in organometallic compounds with a single transition‐metal atom, this mechanism has a geometric site requirement of three adjacent Pt atoms in the form of a three‐fold site. The same geometric site requirement is identified for preferential CH bond cleavage of acetylene with the formation of adsorbed CCH and H species. In the absence of three‐fold Pt sites, the reaction mechanism changes, and reactions of H transfer and CH bond cleavage are suppressed.
A Chimeric Siderophore Halts Swarming Vibrio
Authors: Böttcher Thomas , Clardy Jon 
Published: February 2014

AbstractSome bacteria swarm under some circumstances; they move rapidly and collectively over a surface. In an effort to understand the molecular signals controlling swarming, we isolated two bacterial strains from the same red seaweed, Vibrio alginolyticus B522, a vigorous swarmer, and Shewanella algae B516, which inhibits V. alginolyticus swarming in its vicinity. Plate assays combined with NMR, MS, and X‐ray diffraction analyses identified a small molecule, which was named avaroferrin, as a potent swarming inhibitor. Avaroferrin, a previously unreported cyclic dihydroxamate siderophore, is a chimera of two well‐known siderophores: putrebactin and bisucaberin. The sequenced genome of S. algae revealed avaroferrin’s biosynthetic gene cluster to be a mashup of putrebactin and bisucaberin biosynthetic genes. Avaroferrin blocks swarming through its ability to bind iron in a form that cannot be pirated by V. alginolyticus, thereby securing this essential resource for its producer.
Polyhydroxybutyrate and hydroxyvalerate production by Bacillus megaterium strain A1 isolated from hydrocarbon‐contaminated soil
Authors: Güngörmedi Gökhan , Demirbilek Murat , Mutlu M. Burçin , Denkbaş Emir Baki , Çabuk Ahmet 
Published: February 2014

ABSTRACTIn this study, we attempted to find an alternative microbial resource as a bioplastic producer. Among all of the isolates, the A1 strain produced 44% poly(β‐hydroxybutyrate) (PHB) in proportion to its dry cell weight. The molecular identification of the 16S RNA gene showed that this bacterium was a strain of Bacillus megaterium with the accession number KC579390. The optimization studies led us to the conclusion that the highest poly(β‐hydroxybutyrate‐co‐hydroxyvalerate) (PHBV) production was 78% when 5% molasses was used as the carbon source at pH 6 and 35°C after 60 h of incubation. Attenuated total reflectance Fourier transform infrared (FTIR) spectroscopy and H‐NMR were used for chemical characterization. Differential scanning calorimetry was used to determine the thermal properties of the PHB and PHBV that were synthesized with sucrose and molasses as carbon sources, respectively. The FTIR spectra of the polymers were characterized by typical absorption bands at 1715–1720 cm−1 for amide‐bound CO bands and 1261–1279 cm−1 for an ester‐bound CO band. The molecular weights of PHB and PHBV synthesized with sucrose and molasses were calculated as 428 and 498 kDa, respectively, according to the viscometric method. This study indicated that the B. megaterium strain A1 is an alternative microbial resource as a bioplastic producer. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40530.
On the non‐newtonian viscous behavior of polymer melts in terms of temperature and pressure‐dependent hole fraction
Authors: Dinc Fatma Sahin , Sedlacek Tomas , Tav Cumali , Yahsi Ugur 
Published: February 2014

ABSTRACTA new theoretical non‐Newtonian viscosity model is developed by taking the fractional series expansion of Eyring's shearing strain rate. A broad range of experimental rheological data of various polymer melts including polyethylenes, polypropylene, polystyrene, poly (methyl methacrylate), and polycarbonate are fitted well using the proposed model. From the model; zero shear, constant shear‐stress and constant shear‐rate viscosities are derived as a linear function of viscosity related quantity, Yh, called “thermo‐occupancy function” and their coefficients are discussed in detail. The thermo‐occupancy function is expressed in terms of temperature and structural vacancies such as hole fraction computed from the Simha‐Somcynsky Hole Theory (SS). In addition, the derivative of the logarithm of viscosities with respect to the hole fraction, named as viscoholibility, is observed decreases with the increasing hole fraction. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40540.
Fishermen's perception on the sustainability of small‐scale fisheries and dolphin–fisheries interactions in two increasingly fragile coastal ecosystems in western Greece
Authors: Gonzalvo Joan , Giovos Ioannis , Moutopoulos Dimitrios K. 
Published: February 2014

Abstract

Despite their geographic proximity, the Gulf of Ambracia and the Inner Ionian Sea Archipelago are remarkably different in terms of environmental features, human activities, and dolphin species composition and densities.
Interviews of small‐scale professional fishermen (n = 100) showed that younger generations do not see any future in fisheries and that the traditionally‐oriented fishing community is rapidly changing.
Fish captures have reportedly decreased dramatically during the last 20 years. The main factors having an adverse impact on the sustainability of small‐scale fisheries differed significantly between areas.
Net damage as a consequence of dolphin predation was almost unanimously reported. Hence, fishermen seemed genuinely interested in collaborating in future research initiatives to evaluate the damage caused by dolphins and to explore potential mitigation strategies.
Dolphins were not the only animals held responsible for net damage, nor those reportedly causing the largest economic loss to small‐scale fisheries, which was attributed to either sea turtles or the critically endangered monk seal, depending on the area.
The fishermen of the Gulf of Ambracia advocated the introduction of measures to curtail habitat degradation as the top priority, while their colleagues of the Inner Ionian Sea Archipelago identified fisheries management measures and effective law enforcement as the most urgently needed actions.
Given the high dependency of local communities on fisheries, ensuring their sustainability is crucial to providing local fishers with sufficient income. The top management measures identified by local small‐scale fishermen perfectly match the priorities set out within the Natura 2000 network, achievable through an ecosystem‐based approach. Failure to take action in a timely manner may lead to irreversible environmental damage coupled with the need for harsher regulatory measures. Copyright © 2014 John Wiley & Sons, Ltd.