bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overexpression of DJ‐1/PARK7, the Parkinson's disease‐related protein, improves mitochondrial function via Akt phosphorylation on threonine 308 in dopaminergic neuron‐like cells
Authors: Zhang Yi , Gong Xiao‐Gang , Wang Zhen‐Zhen , Sun Hong‐Mei , Guo Zhen‐Yu , Hu Jing‐Hong , Ma Ling , Li Ping , Chen Nai‐Hong 
Published: February 2016

AbstractDJ‐1/PARK7, the Parkinson's disease‐related protein, plays an important role in mitochondrial function. However, the mechanisms by which DJ‐1 affects mitochondrial function are not fully understood. Akt is a promoter of neuron survival and is partly involved in the neurodegenerative process. This research aimed at investigating a possible relationship between DJ‐1 and Akt signalling in regulating mitochondrial function in the dopaminergic neuron‐like cells SH‐SY5Y and PC‐12. Overexpression of DJ‐1 was firstly validated at both the transcriptional and translational levels after transit transfection with plasmid pcDNA3‐Flag‐DJ‐1. Confocal fluorescence microscopy demonstrated that overexpression of DJ‐1 increased the mitochondrial mass, but did not disrupt the mitochondrial morphology. In addition, mitochondrial complex I activity was raised in DJ‐1‐overexpressing cells, and this rise occurred with an increase in cellular adenosine 5′‐triphosphate content. Moreover, immunoblotting demonstrated that the levels of phosphoinositide 3‐kinase and the total Akt were not altered in DJ‐1‐overexpressing cells, and nor was the Akt phosphorylation on serine 473 changed. By contrast, Akt phosphorylation on threonine 308 was significantly augmented by overexpression of DJ‐1, and the expression of glycogen synthase kinase‐3beta, a downstream effector of Akt, was suppressed. In summary, these results suggest that overexpression of DJ‐1 improves the mitochondrial function, at least in part, through a mechanism involving Akt phosphorylation on threonine 308.
Rest tremor in idiopathic adult‐onset dystonia
Authors: Gigante A. F. , Berardelli A. , Defazio G. 
Published: February 2016

BackgroundTremor in dystonia has been described as a postural or kinetic abnormality. In recent series, however, patients with idiopathic adult‐onset dystonia also displayed rest tremor.MethodsThe frequency and distribution of rest tremor were studied in a cohort of 173 consecutive Italian patients affected by various forms of idiopathic adult‐onset dystonia attending our movement disorder clinic over 8 months.ResultsExamination revealed tremor in 59/173 patients (34%): 12 patients had head tremor, 34 patients had arm tremor, whilst 13 patients presented tremor in both sites. Head tremor was postural in all patients, whereas arm tremor was postural/kinetic in 28 patients, only at rest in one and both postural/kinetic and at rest in 18 patients. Patients with tremor were more likely to have segmental/multifocal dystonia. Patients who had rest tremor (either alone or associated with action tremor) had a higher age at dystonia onset and a greater frequency of dystonic arm involvement than patients with action tremor alone or without tremor.ConclusionsBoth action and rest tremor are part of the tremor spectrum of adult‐onset dystonia and are more frequently encountered in segmental/multifocal dystonia. The higher age at dystonia onset and the greater frequency of arm dystonia in patients with rest tremor may have pathophysiological implications and may account, at least in part, for the previous lack of identification of rest tremor as one possible type of tremor present in dystonia.
Does serum uric acid act as a modulator of cerebrospinal fluid Alzheimer's disease biomarker related cognitive decline?
Authors: Ye B. S. , Lee W. W. , Ham J. H. , Lee J. J. , Lee P. H. , Sohn Y. H. ,   the Alzheimer's Disease Neuroimaging Initiative
Published: February 2016

Background and purposeThe association of serum uric acid, cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) and longitudinal cognitive decline was evaluated using the AD Neuroimaging Initiative database.MethodsIn 271 healthy subjects, 596 mild cognitive impairment patients and 197 AD patients, serum uric acid and CSF AD biomarkers were measured at baseline, and Mini‐Mental State Examination and AD Assessment Scale − Cognitive Subscale (ADAS‐cog) were assessed serially (mean duration, 2.9 years). The effect of uric acid on longitudinal cognitive decline was evaluated using linear mixed effect models for Mini‐Mental State Examination and ADAS‐cog scores in female and male subjects separately, with possible confounders controlled (model 1). To determine the effects of uric acid independent of CSF biomarker (Aβ1–42 or tau) and to test whether the detrimental effects of CSF biomarker differ according to uric acid, CSF biomarker and its interaction with uric acid were further included in model 1 (model 2).ResultsHigher levels of uric acid were associated with slower cognitive decline, particularly in the mild cognitive impairment and dementia subgroups, and more prominently in female subjects. Model 2 with CSF Aβ1–42 showed that higher levels of uric acid were associated with a slower cognitive decline and alleviated the detrimental effect of Aβ1–42 on cognitive decline. Model 2 with CSF tau showed that higher levels of uric acid alleviated the detrimental effect of tau on cognitive decline in female subjects but not in male subjects.ConclusionHigher levels of uric acid had protective effects on longitudinal cognitive decline independent of and interactively with CSF AD biomarkers.
Mislocalization of syntaxin‐1 and impaired neurite growth observed in a human iPSC model for STXBP1‐related epileptic encephalopathy
Authors: Yamashita Satoshi , Chiyonobu Tomohiro , Yoshida Michiko , Maeda Hiroshi , Zuiki Masashi , Kidowaki Satoshi , Isoda Kenichi , Morimoto Masafumi , Kato Mitsuhiro , Saitsu Hirotomo , Matsumoto Naomichi , Nakahata Tatsutoshi , Saito Megumu K. , Hosoi Hajime 
Published: February 2016

SummarySyntaxin‐binding protein 1 (STXBP1) is essential for synaptic vesicle exocytosis. Mutations of its encoding gene, STXBP1, are among the most frequent genetic causes of epileptic encephalopathies. However, the precise pathophysiology of STXBP1 haploinsufficiency has not been elucidated. Using patient‐derived induced pluripotent stem cells (iPSCs), we aimed to establish a neuronal model for STXBP1 haploinsufficiency and determine the pathophysiologic basis for STXBP1 encephalopathy. We generated iPSC lines from a patient with Ohtahara syndrome (OS) harboring a heterozygous nonsense mutation of STXBP1 (c.1099C>T; p.R367X) and performed neuronal differentiation. Both STXBP1 messenger RNA (mRNA) and STXBP1 protein expression levels of OS‐derived neurons were approximately 50% lower than that of control‐derived neurons, suggesting that OS‐derived neurons are a suitable model for elucidating the pathophysiology of STXBP1 haploinsufficiency. Through Western blot and immunocytochemistry assays, we found that OS‐derived neurons show reduced levels and mislocalization of syntaxin‐1, a component of soluble N‐ethylmaleimide‐sensitive factor attachment receptor (SNARE) proteins. In addition, OS‐derived neurons have impaired neurite outgrowth. In conclusion, this model enables us to investigate the neurobiology of STXBP1 encephalopathy throughout the stages of neurodevelopment. Reduced expression of STXBP1 leads to changes in the expression and localization of syntaxin‐1 that may contribute to the devastating phenotype of STXBP1 encephalopathy.
Structural and kinetic studies on RosA, the enzyme catalysing the methylation of 8‐demethyl‐8‐amino‐d‐riboflavin to the antibiotic roseoflavin
Authors: Tongsook Chanakan , Uhl Michael K. , Jankowitsch Frank , Mack Matthias , Gruber Karl , Macheroux Peter 
Published: February 2016

N,N‐8‐demethyl‐8‐amino‐d‐riboflavin dimethyltransferase (RosA) catalyses the final dimethylation of 8‐demethyl‐8‐amino‐d‐riboflavin (AF) to the antibiotic roseoflavin (RoF) in Streptomyces davawensis. In the present study, we solved the X‐ray structure of RosA, and determined the binding properties of substrates and products. Moreover, we used steady‐state and rapid reaction kinetic studies to obtain detailed information on the reaction mechanism. The structure of RosA was found to be similar to that of previously described S‐adenosylmethionine (SAM)‐dependent methyltransferases, featuring two domains: a mainly α‐helical ‘orthogonal bundle’ and a Rossmann‐like domain (α/β twisted open sheet). Bioinformatics studies and molecular modelling enabled us to predict the potential SAM and AF binding sites in RosA, suggesting that both substrates, AF and SAM, bind independently to their respective binding pocket. This finding was confirmed by kinetic experiments that demonstrated a random‐order ‘bi‐bi’ reaction mechanism. Furthermore, we determined the dissociation constants for substrates and products by either isothermal titration calorimetry or UV/Vis absorption spectroscopy, revealing that both products, RoF and S‐adenosylhomocysteine (SAH), bind more tightly to RosA compared with the substrates, AF and SAM. This suggests that RosA may contribute to roseoflavin resistance in S. davawensis. The tighter binding of products is also reflected by the results of inhibition experiments, in which RoF and SAH behave as competitive inhibitors for AF and SAM, respectively. We also showed that formation of a ternary complex of RosA, RoF and SAH (or SAM) leads to drastic spectral changes that are indicative of a hydrophobic environment.DatabaseStructural data are available in the Protein Data Bank under accession number 4D7K.
General time‐dependent C(t) and J(t) estimation equations for elastic‐plastic‐creep fracture mechanics analysis
Authors: Lee H.‐S. , Je J.‐H. , Kim Y.‐J. , Ainsworth R. A. , Budden P. J. 
Published: February 2016

AbstractThis paper presents equations for estimating the crack tip characterizing parameters C(t) and J(t), for general elastic‐plastic‐creep conditions where the power‐law creep and plasticity stress exponents differ, by modifying the plasticity correction term in published equations. The plasticity correction term in the newly proposed equations is given in terms of the initial elastic‐plastic and steady‐state creep stress fields. The predicted C(t) and J(t) results are validated by comparison with systematic elastic‐plastic‐creep FE results. Good agreement with the FE results is found.
Contributions of airborne dispersal and dormant propagule recruitment to the assembly of rotifer and crustacean zooplankton communities in temporary ponds
Authors: Lopes Paloma M. , Bozelli Reinaldo , Bini Luis M. , Santangelo Jayme M. , Declerck Steven A. J. 
Published: February 2016

Summary

Metacommunity theory assumes that communities are not only affected by local processes but also interact with each other through dispersal. It is generally assumed that zooplankton can quickly recolonise water bodies after droughts, via both dormant egg banks and dispersal of resting eggs. Hitherto, few studies have evaluated the relative importance of resting egg bank recruitment and airborne dispersal in the re‐establishment of zooplankton communities.

As zooplankton communities of temporary ponds are frequently confronted by dry phases and have the potential to build up large resting egg banks, we expected the contribution of such resting egg bank to be more important than airborne dispersal for community re‐establishment after drought. We also expected that the relative importance of airborne dispersal would be higher for rotifers than for microcrustaceans, as the former group has key traits (e.g. smaller body sizes, shorter generation times and higher reproductive potential) that are thought to enhance the dispersal to and colonisation of vacant habitat.

We performed an enclosure experiment in the vicinity of seven temporary ponds, simulating the colonisation by zooplankton exclusively via the resting egg bank, exclusively via airborne dispersal and via both pathways simultaneously. The enclosures were sampled five times during a period of 53 days.

Our results show that zooplankton organisms were able to rapidly colonise the experimental enclosures, either through their resting egg bank or by airborne dispersal of resting eggs. However, microcrustaceans tended to rely more on recolonisation from the resting egg banks than rotifers, at least for the spatial and temporal scales considered in our study.
Variations in soil carbon sequestration and their determinants along a precipitation gradient in seasonally dry tropical forest ecosystems
Authors: Campo Julio , Merino Agustín 
Published: February 2016

AbstractThe effect of precipitation regime on the C cycle of tropical forests is poorly understood, despite the existence of models that suggest a drier climate may substantially alter the source‐sink function of these ecosystems. Along a precipitation regime gradient containing 12 mature seasonally dry tropical forests growing under otherwise similar conditions (similar annual temperature, rainfall seasonality, and geological substrate), we analyzed the influence of variation in annual precipitation (1240 to 642 mm) and duration of seasonal drought on soil C. We investigated litterfall, decomposition in the forest floor, and C storage in the mineral soil, and analyzed the dependence of these processes and pools on precipitation. Litterfall decreased slightly – about 10% – from stands with 1240 mm yr−1to those with 642 mm yr−1, while the decomposition decreased by 56%. Reduced precipitation strongly affected C storage and basal respiration in the mineral soil. Higher soil C storage at the drier sites was also related to the higher chemical recalcitrance of litter (fine roots and forest floor) and the presence of charcoal across sites, suggesting an important indirect influence of climate on C sequestration. Basal respiration was controlled by the amount of recalcitrant organic matter in the mineral soil. We conclude that in these forest ecosystems, the long‐term consequences of decreased precipitation would be an increase in organic layer and mineral soil C storage, mainly due to lower decomposition and higher chemical recalcitrance of organic matter, resulting from changes in litter composition and, likely also, wildfire patterns. This could turn these seasonally dry tropical forests into significant soil C sinks under the predicted longer drought periods if primary productivity is maintained.
The permafrost carbon inventory on the Tibetan Plateau: a new evaluation using deep sediment cores
Authors: Ding Jinzhi , Li Fei , Yang Guibiao , Chen Leiyi , Zhang Beibei , Liu Li , Fang Kai , Qin Shuqi , Chen Yongliang , Peng Yunfeng , Ji Chengjun , He Honglin , Smith Pete , Yang Yuanhe 
Published: February 2016

AbstractThe permafrost organic carbon (OC) stock is of global significance because of its large pool size and the potential positive feedback to climate warming. However, due to the lack of systematic field observations and appropriate upscaling methodologies, substantial uncertainties exist in the permafrost OC budget, which limits our understanding of the fate of frozen carbon in a warming world. In particular, the lack of comprehensive estimates of OC stocks across alpine permafrost means that current knowledge on this issue remains incomplete. Here, we evaluated the pool size and spatial variations of permafrost OC stock to 3 m depth on the Tibetan Plateau by combining systematic measurements from a substantial number of pedons (i.e. 342 three‐metre‐deep cores and 177 50‐cm‐deep pits) with a machine learning technique (i.e. support vector machine, SVM). We also quantified uncertainties in permafrost carbon budget by conducting Monte Carlo simulations. Our results revealed that the combination of systematic measurements with the SVM model allowed spatially explicit estimates to be made. The OC density (OC amount per unit area, OCD) exhibited a decreasing trend from the south‐eastern to the north‐western plateau, with the exception that OCD in the swamp meadow was substantially higher than that in surrounding regions. Our results also demonstrated that Tibetan permafrost stored a large amount of OC in the top 3 m, with the median OC pool size being 15.31 Pg C (interquartile range: 13.03–17.77 Pg C). 44% of OC occurred in deep layers (i.e. 100–300 cm), close to the proportion observed across the northern circumpolar permafrost region. The large carbon pool size together with significant permafrost thawing suggests a risk of carbon emissions and positive climate feedback across the Tibetan alpine permafrost region.
TDP‐43 binds and transports G‐quadruplex‐containing mRNAs into neurites for local translation
Authors: Ishiguro Akira , Kimura Nobuyuki , Watanabe Yuto , Watanabe Sumiko , Ishihama Akira 
Published: February 2016

Growth and differentiation of the neurites depends on long‐distance transport of a specific set of mRNAs to restricted area and their local translation. Here, we found that a TAR DNA‐binding protein of 43 kDa in size (TDP‐43) plays an essential role in intracellular transport of mRNA. For identification of target RNAs recognized by TDP‐43, we purified TDP‐43 in soluble dimer form and subjected to in vitro systematic evolution of ligands by exponential enrichment (SELEX) screening. All the TDP‐43‐bound RNAs were found to contain G‐quadruplex (G4). Using a double‐fluorescent probe system, G4‐containing RNAs were found to be transported, together with TDP‐43, into the distal neurites. Two lines of evidence indicated that loss of function of TDP‐43 results in the neurodegenerative disorder: (i) amyotrophic lateral sclerosis (ALS)‐linked mutant TDP‐43M337V lacks the activity of binding and transport of G4‐containing mRNAs; and (ii) RNA containing G4‐forming GGGGCC repeat expansion from the ALS‐linked C9orf72 gene absorbs TDP‐43, thereby reducing the intracellular pool of functional TDP‐43. Taken together, we propose that TDP‐43 within neurons plays an essential role of mRNA transport into distal neurites for local translation, and thus, dysfunctions of TDP‐43 cause neural diseases such as ALS and frontotemporal lobar degeneration.
Characterization of five associations of F8 missense mutations containing FVIII B domain mutations
Authors: Jourdy Y. , Nougier C. , Roualdes O. , Fretigny M. , Durand B. , Negrier C. , Vinciguerra C. 
Published: February 2016

IntroductionHaemophilia A (HA) is a bleeding disorder due to an absence or a reduced activity of coagulation factor VIII (FVIII) caused by mutations in F8 gene. Missense mutations represent approximately 45% of the reported molecular defects in HA. However, only few missense mutations in FVIII B domain have been described.AimThe aim of this study was to characterize five genetic variations (three novels and two previously reported) localized in the FVIII B domain. In all cases, an additional missense variation located outside the FVIII B domain was found. We investigated each of these variations separately and in combination too for their contribution to HA phenotype.MethodsF8 variants were transiently expressed in COS‐1 cells. Media and cell lysates were collected after 72 h. Then, FVIII activity, secretion and thermostability were analysed and compared to FVIII wild‐type.ResultsThe 5 FVIII B domain variants showed normal FVIII:C (98.5–128.5%) and FVIII:Ag (97.7–154%). No synergistic effect was observed between the B domain variant and their associated mutations. In contrast, the variants located outside the B domain, p.V682L, p.S714L, p.V592D and p.C573F revealed significantly decrease of FVIII:C with values in the range 3.5–44.5% (p < 0.05). However, the p.G224R variant showed FVIII:C and FVIII:Ag values no significantly different from FVIII‐WT.ConclusionThe FVIII B domain variants, p.D963N, p.S806T, p.G873D, p.H998Q and p.Q1225R may be considered as polymorphism or non‐pathologic mutations. In five patients, clinical phenotype could be explained by the additional causative missense mutation. For the p.G224T variant further splicing studies are necessary to determine its pathogenicity.
Short‐distance attraction of saproxylic Heteroptera to olfactory cues
Authors: Koban Marcel B. , Gossner Martin M. , Müller Jörg , Steidle Johannes L. M. , Bässler Claus , Hothorn Torsten , Unsicker Sybille B. , Seibold Sebastian 
Published: February 2016

Abstract

As dead wood is ephemeral, saproxylic insect species must be able to effectively locate new resources via, e.g. olfactory cues.

Although saproxylic flat bugs feed on fungal mycelia, published evidence points to their use of dead wood‐specific volatile cues rather than fungal‐specific cues for long‐distance orientation towards new habitat patches.

To evaluate which olfactory cues saproxylic flat bugs use for short‐distance orientation, we tested the attraction of Aradus obtectus (Vasarhelyi) to fresh wood, fungal mycelia and fungal fruiting bodies using an olfactometer.

Aradus obtectus individuals were attracted only to fungal mycelia but not to wood or fungal fruiting bodies.

Our results and those of our earlier field experiment testing long‐distance attraction (Seibold et al., ) together suggest that A. obtectus uses cues emitted by dead wood to locate potential resources over long distances, but relies on olfactory cues emitted by mycelia of its host species to locate suitable short‐range microhabitats.
Growth factor release from dentine matrix by pulp‐capping agents promotes pulp tissue repair‐associated events
Authors: Tomson P. L. , Lumley P. J. , Smith A. J. , Cooper P. R. 
Published: February 2016

AbstractAimTo characterize growth factor release from dentine by pulp‐capping agents and to determine the effects of liberated dentine extracellular matrix (dECM) components on pulp cells in the key wound healing processes of migration and cell growth.MethodologyPowdered human dentine was exposed to solutions of calcium hydroxide, white and grey mineral trioxide aggregate (MTA) (ProRoot, (Dentsply Tulsa, Tulsa, OK, USA) over 14 days. The solubilized dECM components were dialysed and lyophilized and characterized using multiplex quantitative ELISA. Following dECM component extraction dentine was analysed using Fourier‐transformed infrared spectroscopy (FTIR). Primary rat dental pulp cells (RDPCs) were exposed to dECM components (0.1–100 μg mL−1) released by calcium hydroxide, white and grey MTA, and cell growth and chemotactic responses were assessed. Statistical differences between the experimental and control groups were determined using one‐way anova.ResultsA broad range of growth factors, many not previously reported in dentine, were liberated by these pulp‐capping agents, including SCF, M‐CSF, GM‐CSF, IGFBP‐1, NGF and GDNF. White and grey MTA liberated more growth factors than calcium hydroxide. FTIR analysis of dentine exposed to pulp‐capping agents showed partial depletion of amide bands I, II and III, with little alteration in phosphate peaks compared to untreated dentine. dECM components released by white and grey MTA induced significantly more cell growth at low‐to‐moderate concentrations (P ≦ 0.05) examined in this study and significantly enhanced cell chemotaxis at all concentrations compared with controls (P ≦ 0.05).ConclusionsWhite and grey MTA solubilize a broad range of bioactive molecules from dentine, which can induce proliferation and chemotaxis in pulp cells.