bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lipid peroxidation is essential for α‐synuclein‐induced cell death
Authors: Angelova Plamena R. , Horrocks Mathew H. , Klenerman David , Gandhi Sonia , Abramov Andrey Y. , Shchepinov Mikhail S. 
Published: January 2015

AbstractParkinson's disease is the second most common neurodegenerative disease and its pathogenesis is closely associated with oxidative stress. Deposition of aggregated α‐synuclein (α‐Syn) occurs in familial and sporadic forms of Parkinson's disease. Here, we studied the effect of oligomeric α‐Syn on one of the major markers of oxidative stress, lipid peroxidation, in primary co‐cultures of neurons and astrocytes. We found that oligomeric but not monomeric α‐Syn significantly increases the rate of production of reactive oxygen species, subsequently inducing lipid peroxidation in both neurons and astrocytes. Pre‐incubation of cells with isotope‐reinforced polyunsaturated fatty acids (D‐PUFAs) completely prevented the effect of oligomeric α‐Syn on lipid peroxidation. Inhibition of lipid peroxidation with D‐PUFAs further protected cells from cell death induced by oligomeric α‐Syn. Thus, lipid peroxidation induced by misfolding of α‐Syn may play an important role in the cellular mechanism of neuronal cell loss in Parkinson's disease.
image
We have found that aggregated α‐synuclein‐induced production of reactive oxygen species (ROS) that subsequently stimulates lipid peroxidation and cell death in neurons and astrocytes. Specific inhibition of lipid peroxidation by incubation with reinforced polyunsaturated fatty acids (D‐PUFAs) completely prevented the effect of α‐synuclein on lipid peroxidation and cell death.
The cytochrome P450 2D‐mediated formation of serotonin from 5‐methoxytryptamine in the brain in vivo: a microdialysis study
Authors: Haduch Anna , Bromek Ewa , Kot Marta , Kamińska Katarzyna , Gołembiowska Krystyna , Daniel Wladyslawa A. 
Published: January 2015

AbstractThe cytochrome P450 2D (CYP2D) mediates synthesis of serotonin from 5‐methoxytryptamine (5‐MT), shown in vitro for cDNA‐expressed CYP2D‐isoforms and liver and brain microsomes. We aimed to demonstrate this synthesis in the brain in vivo. We measured serotonin tissue content in brain regions after 5‐MT injection into the raphe nuclei (Model‐A), and its extracellular concentration in rat frontal cortex and striatum using an in vivo microdialysis (Model‐B) in male Wistar rats. Naïve rats served as control animals. 5‐MT injection into the raphe nuclei of PCPA‐(tryptophan hydroxylase inhibitor)‐pretreated rats increased the tissue concentration of serotonin (from 40 to 90% of the control value, respectively, in the striatum), while the CYP2D inhibitor quinine diminished serotonin level in some brain structures of those animals (Model‐A). 5‐MT given locally through a microdialysis probe markedly increased extracellular serotonin concentration in the frontal cortex and striatum (to 800 and 1000% of the basal level, respectively) and changed dopamine concentration (Model‐B). Quinine alone had no effect on serotonin concentration; however, given jointly with 5‐MT, it prevented the 5‐MT‐induced increase in cortical serotonin in naïve rats and in striatal serotonin in PCPA‐treated animals. These results indicate that the CYP2D‐catalyzed alternative pathway of serotonin synthesis from 5‐MT is relevant in the brain in vivo, and set a new target for the action of psychotropics.
image
The aim of this study was to demonstrate that the cytochrome P450 (CYP2D)‐mediated synthesis of serotonin from 5‐methoxytryptamine (5‐MT) can take place in rat brain in vivo. Intracerebral injection of 5‐MT increased tissue and extracellular serotonin concentration in the brain. Quinine (a CYP2D inhibitor) prevented the 5‐MT‐induced increase in serotonin concentration. The results confirm our hypothesis and indicate that the CYP2D‐catalyzed serotonin synthesis from 5‐MT in the brain can be considered as a new pharmacological target. 5‐HT = 5‐hydroxytryptamine (serotonin); QUIN = quinine. Symbols: *p < 0.01 versus control, ^p < 0.1 versus 5‐MT, !p < 0.01 versus QUIN (repeated measures anova and Tukey's post hoc test).
Dose–responses of zinc–methionine supplements on growth, blood metabolites and gastrointestinal development in sheep
Authors: Jafarpour N. , Khorvash M. , Rahmani H. R. , Pezeshki A. , Hosseini Ghaffari M. 
Published: January 2015

SummaryThe effects of zinc–methionine (Zn‐Met) supplementation on growth, blood metabolites and gastrointestinal development were investigated in two experiments with sheep. The objective of Experiment 1 was to determine the effects of Zn‐Met supplementation on hormones and metabolites involved in growth and energy balance regulation, while Experiment 2 aimed to determine the effects of Zn‐Met on feed intake, body weight, gastrointestinal development and liver glycogen concentration in lamb. The animals were assigned to groups with different concentrations of dietary Zn‐Met (0, 0.4, 0.8 and 1.2 g/day) in both experiments. In Experiment 1, feeding different doses of Zn‐Met increased plasma insulin‐like growth factor 1 (IGF‐1) concentration, but it linearly decreased plasma growth hormone (GH). No differences were observed in blood cortisol, insulin and glucose concentrations among the treatments. In Experiment 2, addition of Zn‐Met to the diets did not lead to changes in the body weights of the lambs. Both average daily gain and dry matter intake (DMI) increased linearly with increasing concentrations of dietary Zn‐Met. Lambs receiving Zn‐Met showed higher liver glycogen concentrations than the control. While significant increases were observed in the villus height and crypt depth in the duodenum and jejunum as a result of Zn‐Met supplementation, no change was detected in blood glucose concentrations (p > 0.05). Our findings suggest that dietary Zn‐Met may improve growth, energy balance and gastrointestinal development in sheep.
Fasting Urinary Calcium‐to‐Creatinine and Oxalate‐to‐Creatinine Ratios in Dogs with Calcium Oxalate Urolithiasis and Breed‐Matched Controls
Authors: Furrow E. , Patterson E.E. , Armstrong P.J. , Osborne C.A. , Lulich J.P. 
Published: January 2015

BackgroundHypercalciuria and hyperoxaluria are risk factors for calcium oxalate (CaOx) urolithiasis, but breed‐specific reports of urinary metabolites and their relationship with stone status are lacking.ObjectiveTo compare urinary metabolites (calcium and oxalate) and blood ionized calcium (iCa) concentrations between CaOx stone formers and breed‐matched stone‐free controls for the Miniature Schnauzer, Bichon Frise, and Shih Tzu breeds.AnimalsForty‐seven Miniature Schnauzers (23 cases and 24 controls), 27 Bichons Frise (14 cases and 13 controls), and 15 Shih Tzus (7 cases and 8 controls).MethodsProspective study. Fasting spot urinary calcium‐to‐creatinine and oxalate‐to‐creatinine ratios (UCa/Cr and UOx/Cr, respectively) and bloodiCa concentrations were measured and compared between cases and controls within and across breeds. Regression models were used to test the effect of patient and environmental factors on these variables.ResultsUCa/Cr was higher in cases than controls for each of the 3 breeds. In addition to stone status, being on a therapeutic food designed to prevent CaOx stone recurrence was associated with higher UCa/Cr. UOx/Cr did not differ between cases and controls for any of the breeds. BloodiCa was higher in cases than controls in the Miniature Schnauzer and Bichon Frise breeds and had a moderate correlation with UCa/Cr.Conclusions and Clinical ImportanceHypercalciuria is associated with CaOx stone status in the Miniature Schnauzer, Bichon Frise, and Shih Tzu breeds.UOx/Cr did not correlate with stone status in these 3 breeds. These findings may influence breed‐specific stone prevention recommendations.
Elusive Counterfactuals
Authors: Lewis Karen S. 
Published: January 2015

AbstractI offer a novel solution to the problem of counterfactual skepticism: the worry that all contingent counterfactuals without explicit probabilities in the consequent are false. I argue that a specific kind of contextualist semantics and pragmatics for would‐ and might‐counterfactuals can block both central routes to counterfactual skepticism. One, it can explain the clash between would‐ and might‐counterfactuals as in: (1) If you had dropped that vase, it would have broken. and (2) If you had dropped that vase, it might have safely quantum tunneled to China. Two, it can explain why counterfactuals like (1) can be true despite the fact that quantum tunneling worlds are among the most similar worlds. I further argue that this brand of contextualism accounts for the data better than other existing solutions to the problem.
Optimal design in pediatric pharmacokinetic and pharmacodynamic clinical studies
Authors: Roberts Jessica K. , Stockmann Chris , Balch Alfred , Yu Tian , Ward Robert M. , Spigarelli Michael G. , Sherwin Catherine M. T. 
Published: January 2015

SummaryIt is not trivial to conduct clinical trials with pediatric participants. Ethical, logistical, and financial considerations add to the complexity of pediatric studies. Optimal design theory allows investigators the opportunity to apply mathematical optimization algorithms to define how to structure their data collection to answer focused research questions. These techniques can be used to determine an optimal sample size, optimal sample times, and the number of samples required for pharmacokinetic and pharmacodynamic studies. The aim of this review is to demonstrate how to determine optimal sample size, optimal sample times, and the number of samples required from each patient by presenting specific examples using optimal design tools. Additionally, this review aims to discuss the relative usefulness of sparse vs rich data. This review is intended to educate the clinician, as well as the basic research scientist, whom plan on conducting a pharmacokinetic/pharmacodynamic clinical trial in pediatric patients.
Platelet‐derived microparticles induce polymorphonuclear leukocyte‐mediated damage of human pulmonary microvascular endothelial cells
Authors: Xie Ru Feng , Hu Ping , Wang Zhi Cheng , Yang Jie , Yang Yi Ming , Gao Li , Fan Hua Hua , Zhu Yong Ming 
Published: January 2015

BackgroundPlatelets (PLTs) stored at 22°C accumulate microparticles and biologic response modifiers (BRMs) that induce inflammatory reactions in transfusion recipients. However, soluble BRMs are fully diluted in the recipient's blood circulation. The mechanisms by which BRMs exert their effects have not been elucidated. The objectives of this study were to determine the effect of PLT microparticles (PMPs) on polymorphonuclear leukocyte (PMN)‐mediated human pulmonary microvascular endothelial cell (HMVEC) damage and determine the role of soluble CD40 ligand (sCD40L).Study Design and MethodsPMPs were isolated from apheresis PLT concentrates. We used a two‐insult in vitro model of HMVEC damage to investigate the effects of PMP and sCD40L and role of apocynin, an inhibitor of PMN respiratory burst. Their priming activities were measured using hydrogen peroxide production. The expression of intercellular cell adhesion molecule‐1 (ICAM‐1) and integrin αM (CD11b) were also determined.ResultsLipopolysaccharide (LPS)‐activated HMVEC damage and PMN respiratory burst depend on the presence of PMP and the concentration of sCD40L. PMP‐induced PMN‐mediated HMVEC damage was significantly reduced by apocynin‐treated PMNs (p < 0.05). The surface expression of ICAM‐1 on HMVEC was increased by LPS stimulation. The expression of CD11b on PMNs was increased by PMP priming. Blocking ICAM‐1 with a monoclonal antibody (MoAb) CD54 significantly reduced HMVEC damage (p < 0.05). The treatment of endothelial cells but not PMN with a MoAb targeting CD40 failed to prevent the HMVEC damage caused by PMPs (p > 0.05).ConclusionPMPs carry a concentrated CD40L signal, promote PMN‐mediated HMVEC damage, and may affect the development of transfusion‐related acute lung injury.
Four dimensional magnetic resonance imaging with retrospective k‐space reordering: A feasibility study
Authors: Liu Yilin , Yin Fang‐Fang , Chen Nan‐kuei , Chu Mei‐Lan , Cai Jing 
Published: January 2015

Purpose:Current four dimensional magnetic resonance imaging (4D‐MRI) techniques lack sufficient temporal/spatial resolution and consistent tumor contrast. To overcome these limitations, this study presents the development and initial evaluation of a new strategy for 4D‐MRI which is based on retrospective k‐space reordering.Methods:We simulated a k‐space reordered 4D‐MRI on a 4D digital extended cardiac‐torso (XCAT) human phantom. A 2D echo planar imaging MRI sequence [frame rate (F) = 0.448 Hz; image resolution (R) = 256 × 256; number of k‐space segments (NKS) = 4] with sequential image acquisition mode was assumed for the simulation. Image quality of the simulated “4D‐MRI” acquired from the XCAT phantom was qualitatively evaluated, and tumor motion trajectories were compared to input signals. In particular, mean absolute amplitude differences (D) and cross correlation coefficients (CC) were calculated. Furthermore, to evaluate the data sufficient condition for the new 4D‐MRI technique, a comprehensive simulation study was performed using 30 cancer patients’ respiratory profiles to study the relationships between data completeness (Cp) and a number of impacting factors: the number of repeated scans (NR), number of slices (NS), number of respiratory phase bins (NP), NKS, F, R, and initial respiratory phase at image acquisition (P0). As a proof‐of‐concept, we implemented the proposed k‐space reordering 4D‐MRI technique on a T2‐weighted fast spin echo MR sequence and tested it on a healthy volunteer.Results:The simulated 4D‐MRI acquired from the XCAT phantom matched closely to the original XCAT images. Tumor motion trajectories measured from the simulated 4D‐MRI matched well with input signals (D = 0.83 and 0.83 mm, and CC = 0.998 and 0.992 in superior–inferior and anterior–posterior directions, respectively). The relationship between Cp and NR was found best represented by an exponential function (, when NS = 30, NP = 6). At a CP value of 95%, the relative error in tumor volume was 0.66%, indicating that NR at a CP value of 95% (NR,95%) is sufficient. It was found that NR,95% is approximately linearly proportional to NP (r = 0.99), and nearly independent of all other factors. The 4D‐MRI images of the healthy volunteer clearly demonstrated respiratory motion in the diaphragm region with minimal motion induced noise or aliasing.Conclusions:It is feasible to generate respiratory correlated 4D‐MRI by retrospectively reordering k‐space based on respiratory phase. This new technology may lead to the next generation 4D‐MRI with high spatiotemporal resolution and optimal tumor contrast, holding great promises to improve the motion management in radiotherapy of mobile cancers.
Microbial Engineering for Aldehyde Synthesis
Authors: Kunjapur Aditya M. , Prather Kristala L. J. 
Published: January 2015

ABSTRACT

Aldehydes are a class of chemicals with many industrial uses. Several aldehydes are responsible for flavors and fragrances present in plants, but aldehydes are not known to accumulate in most natural microorganisms. In many cases, microbial production of aldehydes presents an attractive alternative to extraction from plants or chemical synthesis. During the past 2 decades, a variety of aldehyde biosynthetic enzymes have undergone detailed characterization. Although metabolic pathways that result in alcohol synthesis via aldehyde intermediates were long known, only recent investigations in model microbes such as
Escherichia coli
have succeeded in minimizing the rapid endogenous conversion of aldehydes into their corresponding alcohols. Such efforts have provided a foundation for microbial aldehyde synthesis and broader utilization of aldehydes as intermediates for other synthetically challenging biochemical classes. However, aldehyde toxicity imposes a practical limit on achievable aldehyde titers and remains an issue of academic and commercial interest. In this minireview, we summarize published efforts of microbial engineering for aldehyde synthesis, with an emphasis on
de novo
synthesis, engineered aldehyde accumulation in
E. coli
, and the challenge of aldehyde toxicity.
l
-Lactate Production from Biodiesel-Derived Crude Glycerol by Metabolically Engineered Enterococcus faecalis: Cytotoxic Evaluation of Biodiesel Waste and Development of a Glycerol-Inducible Gene Expression System
Authors: Doi Yuki 
Published: January 2015

ABSTRACT

Biodiesel waste is a by-product of the biodiesel production process that contains a large amount of crude glycerol. To reuse the crude glycerol, a novel bioconversion process using
Enterococcus faecalis
was developed through physiological studies. The
E. faecalis
strain W11 could use biodiesel waste as a carbon source, although cell growth was significantly inhibited by the oil component in the biodiesel waste, which decreased the cellular NADH/NAD
+
ratio and then induced oxidative stress to cells. When W11 was cultured with glycerol, the maximum culture density (optical density at 600 nm [OD
600
]) under anaerobic conditions was decreased 8-fold by the oil component compared with that under aerobic conditions. Furthermore, W11 cultured with dihydroxyacetone (DHA) could show slight or no growth in the presence of the oil component with or without oxygen. These results indicated that the DHA kinase reaction in the glycerol metabolic pathway was sensitive to the oil component as an oxidant. The lactate dehydrogenase (Ldh) activity of W11 during anaerobic glycerol metabolism was 4.1-fold lower than that during aerobic glycerol metabolism, which was one of the causes of low
l
-lactate productivity. The
E. faecalis
pflB
gene disruptant (Δ
pfl
mutant) expressing the

ldhL1
LP

gene produced 300 mM
l
-lactate from glycerol/crude glycerol with a yield of >99% within 48 h and reached a maximum productivity of 18 mM h
−1
(1.6 g liter
−1
h
−1
). Thus, our study demonstrates that metabolically engineered
E. faecalis
can convert crude glycerol to
l
-lactate at high conversion efficiency and provides critical information on the recycling process for biodiesel waste.
Efficient Metabolic Exchange and Electron Transfer within a Syntrophic Trichloroethene-Degrading Coculture of Dehalococcoides mccartyi 195 and Syntrophomonas wolfei
Authors: Mao Xinwei , Stenuit Benoit , Polasko Alexandra , Alvarez-Cohen Lisa 
Published: January 2015

ABSTRACT

Dehalococcoides mccartyi
195 (strain 195) and
Syntrophomonas wolfei
were grown in a sustainable syntrophic coculture using butyrate as an electron donor and carbon source and trichloroethene (TCE) as an electron acceptor. The maximum dechlorination rate (9.9 ± 0.1 μmol day
−1
) and cell yield [(1.1 ± 0.3) × 10
8
cells μmol
−1
Cl
−
] of strain 195 maintained in coculture were, respectively, 2.6 and 1.6 times higher than those measured in the pure culture. The strain 195 cell concentration was about 16 times higher than that of
S. wolfei
in the coculture. Aqueous H
2
concentrations ranged from 24 to 180 nM during dechlorination and increased to 350 ± 20 nM when TCE was depleted, resulting in cessation of butyrate fermentation by
S. wolfei
with a theoretical Gibbs free energy of −13.7 ± 0.2 kJ mol
−1
. Carbon monoxide in the coculture was around 0.06 μmol per bottle, which was lower than that observed for strain 195 in isolation. The minimum H
2
threshold value for TCE dechlorination by strain 195 in the coculture was 0.6 ± 0.1 nM. Cell aggregates during syntrophic growth were observed by scanning electron microscopy. The interspecies distances to achieve H
2
fluxes required to support the measured dechlorination rates were predicted using Fick's law and demonstrated the need for aggregation. Filamentous appendages and extracellular polymeric substance (EPS)-like structures were present in the intercellular spaces. The transcriptome of strain 195 during exponential growth in the coculture indicated increased ATP-binding cassette transporter activities compared to the pure culture, while the membrane-bound energy metabolism related genes were expressed at stable levels.
Anoxygenic Photosynthesis Controls Oxygenic Photosynthesis in a Cyanobacterium from a Sulfidic Spring
Authors: Klatt Judith M. , Al-Najjar Mohammad A. A. , Yilmaz Pelin , Lavik Gaute , de Beer Dirk , Polerecky Lubos 
Published: January 2015

ABSTRACT

Before the Earth's complete oxygenation (0.58 to 0.55 billion years [Ga] ago), the photic zone of the Proterozoic oceans was probably redox stratified, with a slightly aerobic, nutrient-limited upper layer above a light-limited layer that tended toward euxinia. In such oceans, cyanobacteria capable of both oxygenic and sulfide-driven anoxygenic photosynthesis played a fundamental role in the global carbon, oxygen, and sulfur cycle. We have isolated a cyanobacterium,
Pseudanabaena
strain FS39, in which this versatility is still conserved, and we show that the transition between the two photosynthetic modes follows a surprisingly simple kinetic regulation controlled by this organism's affinity for H
2
S. Specifically, oxygenic photosynthesis is performed in addition to anoxygenic photosynthesis only when H
2
S becomes limiting and its concentration decreases below a threshold that increases predictably with the available ambient light. The carbon-based growth rates during oxygenic and anoxygenic photosynthesis were similar. However,
Pseudanabaena
FS39 additionally assimilated NO
3
−
during anoxygenic photosynthesis. Thus, the transition between anoxygenic and oxygenic photosynthesis was accompanied by a shift of the C/N ratio of the total bulk biomass. These mechanisms offer new insights into the way in which, despite nutrient limitation in the oxic photic zone in the mid-Proterozoic oceans, versatile cyanobacteria might have promoted oxygenic photosynthesis and total primary productivity, a key step that enabled the complete oxygenation of our planet and the subsequent diversification of life.
Resistant Microbial Cooccurrence Patterns Inferred by Network Topology
Authors: Peura Sari , Bertilsson Stefan , Jones Roger I. , Eiler Alexander 
Published: January 2015

ABSTRACTAlthough complex cooccurrence patterns have been described for microbes in natural communities, these patterns have scarcely been interpreted in the context of ecosystem functioning and stability. Here we constructed networks from species cooccurrences between pairs of microorganisms which were extracted from five individual aquatic time series, including a dystrophic and a eutrophic lake as well as an open ocean site. The resulting networks exhibited higher clustering coefficients, shorter path lengths, and higher average node degrees and levels of betweenness than those of random networks. Moreover, simulations demonstrated that taxa with a large number of cooccurrences and placement at convergence positions in the network, so-called “hubs” and “bottlenecks,” confer resistance against random removal of “taxa.” Accordingly, we refer to cooccurrences at convergence positions as system-relevant interdependencies, as they, like hubs and bottlenecks, determine network topology. These topology features of the cooccurrence networks point toward microbial community dynamics being resistant over time and thus could provide indicators for the state of ecosystem stability.