bluuebunny/crossref_metadata_2025_split huggingface dataset:
Remarkable impairment of Wnt/β‐catenin signaling in the brains of the mice infected with scrapie agents
Authors: Sun Jing , Wang Hui , Chen Li‐Na , Wang Jing , Lv Yan , Yang Xiao‐Dong , Zhang Bao‐Yun , Tian Chan , Shi Qi , Dong Xiao‐Ping 
Published: November 2015

AbstractPrion diseases are a group of neurodegenerative diseases characterized by neuronal loss and spongiform degeneration, astrogliosis and aggregation of scrapie prion protein (PrPSc) in the central nervous system (CNS). The Wnt signaling pathway is a highly evolutionarily conserved pathway in eukaryotes that regulates cell proliferation, differentiation and survival. Impairment of Wnt/β‐catenin signaling has been reported in the CNS of various neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. To investigate the functional state of Wnt/β‐catenin signaling in the CNS tissues during the progression of prion disease, the components of Wnt/β‐catenin signaling in the brains of the scrapie agents 139A‐ and ME7‐infected mice were evaluated. Compared with the normal controls, the brain levels of phosphor‐β‐catenin (Ser33,37 and Thr41) in 139A‐ and ME7‐infected mice were significantly increased, while those of cyclin D1, which is one of the target genes of Wnt signaling, were decreased. The levels of phosphor‐glycogen synthase kinase‐3β (GSK‐3β) Ser9 were markedly reduced, representing an enhanced GSK‐3β activity in scrapie‐infected mice. Both western blot and immunohistochemical assays revealed a remarkable increase of Dickkopf‐1, the antagonist of Wnt/β‐catenin signaling, in the brains of scrapie‐infected anim‐als, which co‐localized well with the remaining neurons in the immunofluorescent tests. We also observed slightly decreased Wnt‐3 and unchanged disheveled‐3 (Dvl‐3) in the brains of the infected mice. Our data, here, strongly indicate an impairment of Wnt/β‐catenin pathway in the brains of prion disease, which shows a time‐dependent progression along with the incubation period.
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Schematic for the impairment of canonical Wnt signaling during prion infection. The left and right parts represent the normal and prion‐infected situations, respectively. Prion infection or PrPSc accumulation triggers the over‐expression of Dickkopf WNT signaling pathway inhibitor 1 (DKK‐1) and the enhancement of glycogen synthase kinase 3β (GSK‐3β) activity, which subsequently promotes the phosphorylation and degradation of β‐catenin. As a result, the impairment of β‐catenin signaling leads to the down‐regulation of Wnt target genes.
No improvement of neuronal metabolism in the reperfusion phase with melatonin treatment after hypoxic‐ischemic brain injury in the neonatal rat
Authors: Berger Hester R. , Morken Tora Sund , Vettukattil Riyas , Brubakk Ann‐Mari , Sonnewald Ursula , Widerøe Marius 
Published: November 2015

AbstractMitochondrial impairment is a key feature underlying neonatal hypoxic‐ischemic (HI) brain injury and melatonin is potentially neuroprotective through its effects on mitochondria. In this study, we have used 1H and 13C NMR spectroscopy after injection of [1‐13C]glucose and [1,2‐13C]acetate to examine neuronal and astrocytic metabolism in the early reperfusion phase after unilateral HI brain injury in 7‐day‐old rat pups, exploring the effects of HI on mitochondrial function and the potential protective effects of melatonin on brain metabolism. One hour after hypoxia‐ischemia, astrocytic metabolism was recovered and glycolysis was normalized, whereas mitochondrial metabolism in neurons was clearly impaired. Pyruvate carboxylation was also lower in both hemispheres after HI. The transfer of glutamate from neurons to astrocytes was higher whereas the transfer of glutamine from astrocytes to neurons was lower 1 h after HI in the contralateral hemisphere. Neuronal metabolism was equally affected in pups treated with melatonin (10 mg/kg) immediately after HI as in vehicle treated pups indicating that the given dose of melatonin was not capable of protecting the neuronal mitochondria in this early phase after HI brain injury. However, any beneficial effects of melatonin might have been masked by modulatory effects of the solvent dimethyl sulfoxide on cerebral metabolism.
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Neuronal and astrocytic metabolism was examined by 13C and 1H NMR spectroscopy in the early reperfusion phase after unilateral hypoxic‐ischemic brain injury and melatonin treatment in neonatal rats. One hour after hypoxia‐ischemia astrocytic mitochondrial metabolism had recovered and glycolysis was normalized, whereas mitochondrial metabolism in neurons was impaired. Melatonin treatment did not show a protective effect on neuronal metabolism.
Striatal adenosine–cannabinoid receptor interactions in rats over‐expressing adenosine A2A receptors
Authors: Chiodi Valentina , Ferrante Antonella , Ferraro Luca , Potenza Rosa Luisa , Armida Monica , Beggiato Sarah , Pèzzola Antonella , Bader Michael , Fuxe Kjell , Popoli Patrizia , Domenici Maria Rosaria 
Published: November 2015

AbstractAdenosine A2A receptors (A2ARs) and cannabinoid CB1 receptors (CB1Rs) are highly expressed in the striatum, where they functionally interact and form A2A/CB1 heteroreceptor complexes. We investigated the effects of CB1R stimulation in a transgenic rat strain over‐expressing A2ARs under the control of the neural‐specific enolase promoter (NSEA2A rats) and in age‐matched wild‐type (WT) animals. The effects of the CB1R agonist WIN 55,212‐2 (WIN) were significantly lower in NSEA2A rats than in WT animals, as demonstrated by i) electrophysiological recordings of synaptic transmission in corticostriatal slices; ii) the measurement of glutamate outflow from striatal synaptosomes and iii) in vivo experiments on locomotor activity. Moreover, while the effects of WIN were modulated by both A2AR agonist (CGS 21680) and antagonists (ZM 241385, KW‐6002 and SCH‐442416) in WT animals, the A2AR antagonists failed to influence WIN‐mediated effects in NSEA2A rats. The present results demonstrate that in rats with genetic neuronal over‐expression of A2ARs, the effects mediated by CB1R activation in the striatum are significantly reduced, suggesting a change in the stoichiometry of A2A and CB1 receptors and providing a strategy to dissect the involvement of A2AR forming or not forming heteromers in the modulation of striatal functions. These findings add additional evidence for the existence of an interaction between striatal A2ARs and CB1Rs, playing a fundamental role in the regulation of striatal functions.
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We studied A2A‐CB1 receptor interaction in transgenic rats over‐expressing adenosine A2A receptors under the control of the neuron‐specific enolase promoter (NSEA2A). In these rats, we demonstrated a reduced effect of the CB1 receptor agonist WIN 55,212‐2 in the modulation of corticostriatal synaptic transmission and locomotor activity, while CB1 receptor expression level did not change with respect to WT rats. A reduction in the expression of A2A‐CB1 receptor heteromers is postulated.Read the Editorial Highlight for this article on page 897.
The development of a questionnaire to evaluate rheumatoid arthritis patient's knowledge about methotrexate
Authors: Fayet Françoise , Savel Carine , Rodere Malory , Pereira Bruno , Abdi Dihya , Mathieu Sylvain , Tournadre Anne , Soubrier Martin , Dubost Jean‐Jacques 
Published: November 2015

Aims and objectivesAssess knowledge concerning methotrexate in rheumatoid arthritis patients by means of a questionnaire.BackgroundMethotrexate is the standard drug for rheumatoid arthritis treatment. It has potentially serious side effects that can be largely prevented by making sure that patients are well informed and comply with prescription guidelines.DesignCross‐sectional survey.MethodsA questionnaire on methotrexate (mode of action, administration, drug interactions), side effects, monitoring and lifestyle implications was offered to all the rheumatoid arthritis patients treated with the drug seen between March and September 2013 in a large hospital in France.ResultsOne hundred and eighty‐three patients (143 women), mean age 60 (13·5) years, with a median disease duration of 12 years [7–20] and treated with methotrexate for eight years [5–13] took part. Methotrexate was identified as a disease‐modifying antirheumatic drug by 78% of the patients. The weekly administration method was well assimilated (97%); 67% indicated that the rationale for folic acid was to reduce treatment toxicity. Only 21% knew that trimethoprim was contraindicated. Half were aware of the haematologic risk and 36% were aware of the risk of hypersensitivity pneumonitis. There was knowledge concerning laboratory testing (80%), but 54% thought they were only being monitored for rheumatoid arthritis activity. Only 13% of the men, but 90% of the women, of childbearing age knew that contraception was essential, and 75% indicated that alcohol consumption should be limited. A low knowledge score correlated significantly with age and low educational level. It was independent of sex, duration of treatment for rheumatoid arthritis.ConclusionsRheumatoid arthritis patient's knowledge concerning methotrexate is poor, particularly for the most serious side effects (haematologic and hypersensitivity pneumonitis), interactions with trimethoprim, and in men, the need for contraception.Relevance to clinical practicePatient knowledge concerning methotrexate should be regularly checked and supported using the different therapeutic education tools available, especially when patients are older people and have had limited schooling.
Global DNA hypomethylation is associated with the development and poor prognosis of tongue squamous cell carcinoma
Authors: Chen Hung‐Chih , Yang Cheng‐Mei , Cheng Jiin‐Tsuey , Tsai Kuo‐Wang , Fu Ting‐Ying , Liou Huei‐Han , Tseng Hui‐Hwa , Lee Jang‐Hwa , Li Guan‐Cheng , Wang Jyh‐Seng , Hou Yu‐Yi , Weng Ta‐Jung , Ger Luo‐Ping 
Published: November 2015

BackgroundsOral cancer is the 4th leading cause of cancer death for males and the top cancer in young adult males in Taiwan. Tongue squamous cell carcinoma (TSCC) is a common oral cancer and generally associated with poor prognosis. Global DNA hypomethylation at the 5 position of cytosine (5mC) is a well‐known epigenetic feature of cancer. Therefore, the purpose of this study was to investigate the relationship of the global 5mC content with the tumorigenesis and prognosis of patients with TSCC.MethodsThe levels of global 5mC were evaluated by immunohistochemistry using tissue microarray slides of 248 surgically resected TSCC and 202 corresponding tumor adjacent normal (TAN) tissues.ResultsWe found that the level of 5mC in TSCC (P < 0.001) was significantly decreased as compared to TAN. Among TSCC tissues, decreased levels of 5mC were associated with female gender (P = 0.036). In addition, the global hypomethylation was associated with the poor disease‐specific survival in TSCC patients (adjusted hazard ratio: 1.55, P = 0.043), especially for patients in older age group (> 50 years, P = 0.013), with moderate or poor cell differentiation (P = 0.044), early stage of disease (I‐II, P = 0.046), small tumor size (T1–T2, P = 0.005), without lymph node involvement (P = 0.041), and ever received postoperative radiotherapy (P = 0.009).ConclusionsGlobal hypomethylation was an independent biomarker for the development and poor prognosis of TSCC.
E‐cadherin regulators are differentially expressed in the epithelium and stroma of keratocystic odontogenic tumors
Authors: Porto Lia Pontes Arruda , dos Santos Jean Nunes , Ramalho Luciana Maria Pedreira , Figueiredo Andreia Leal , Carneiro Júnior Bráulio , Gurgel Clarissa Araújo , Paiva Katiúcia Batista Silva , Xavier Flávia Caló Aquino 
Published: November 2015

BackgroundThe epithelial–mesenchymal transition (EMT) is the process where cells lose their epithelial features and acquire properties of typical mesenchymal cells. The dissociation of tumor cells due to changes in cell–cell adhesion is one of the key principles of tumor invasion and EMT. Thus, the knowledge of the molecular features of EMT in keratocyst odontogenic tumor (KOT) can provide useful markers to aid in the diagnosis and prognosis and perhaps contribute to an alternative therapeutic approach as it shows an aggressive clinical behavior and high recurrence rates. This study aimed to evaluate the EMT in KOT by the immunoexpression of E‐cadherin, N‐cadherin, Snail, and Slug and comparing to radicular cysts and dental follicles.MethodsThirty‐two KOTs, 15 radicular cysts, and 08 dental follicles were used for immunohistochemistry, evaluating the extent, intensity, labeling pattern, cellular compartment in the epithelium and stroma, and the presence of inflammation.ResultsE‐cadherin was preserved in most cases of keratocystic odontogenic tumor. N‐cadherin was increased in the tumor epithelium, a result that was positively correlated with the heterogeneous and nuclear immunoexpression of Slug in the epithelium; Slug also correlated with high Snail immunoexpression. N‐cadherin was positively correlated with Slug in the stroma of keratocystic odontogenic tumors.ConclusionsThe high immunoexpression of Snail and nuclear Slug in keratocystic odontogenic tumors suggests these proteins as transcription factors without necessarily participating in ‘cadherin switching’. However, the knowledge of their induction of the epithelial–mesenchymal transition in odontogenic tumors is still limited.
New Host Record of Myrothecium roridum Causing Leaf Spot on Abutilon megapotamicum from China
Authors: Ben Hai‐Yan , Gao Wei , Qu Hong‐Yun , Chai A‐Li , Shi Yan‐Xia , Xie Xue‐Wen , Li Bao‐Ju 
Published: November 2015

AbstractDuring September 2010, Abutilon megapotamicum plants with dark‐brown concentric spots on leaves were observed in a commercial glasshouse located in Beijing, China. This study was carried out to identify the causal agent of this disease based on Koch's postulates and morphological characteristics. Pathogenicity tests in the glasshouse showed that Myrothecium roridum Tode ex Fr. caused the leaf spot on A. megapotamicum plants, which were the same as those observed in naturally infected plants in the field. Moreover, to confirm the pathogen to species, the rDNA internal transcribed spacer (ITS) of isolate was PCR‐amplified using ITS1 and ITS4 primer pairs and sequenced. DNA analysis revealed a 100% species identity index for M. roridum. To the best of our knowledge, this is the first report of M. roridum on A. megapotamicum in China.
Differentiation and Classification of Phytoplasmas Associated with Almond and GF‐677 Witches'‐Broom Diseases using rRNA and rp Genes
Authors: Motamedi Ehsan , Salehi Mohammad , Sabbagh Seyed Kazem , Salari Mohammad 
Published: November 2015

AbstractStone fruits are affected by several diseases associated with plant pathogenic phytoplasmas. Previous studies have been shown that phytoplasma agents of almond and GF‐677 witches'‐broom (AlmWB and GWB, respectively) diseases belong to pigeon pea witches'‐broom (16SrIX) phytoplasma group. In this study, partial biological and molecular characterization was used to compare and classify phytoplasma agents of Khafr AlmWB (KAlmWB) and Estahban GWB (EGWB) diseases. Production of different symptoms in periwinkle indicated that agents of KAlmWB and EGWB are differentiable. Expected fragments were amplified from diseased almond and GF‐677 trees in direct PCR using phytoplasma universal primer pairs P1/P7 and rpF1/rpR1 and nested PCR using P1/P7 followed by R16F2n/ R16R2 primer pair. 16S‐rDNA Restriction fragment length polymorphism (RFLP) as well as phylogenetic analysis of rplV‐rpsC and 16S–23S rRNA spacer region sequences classified KAlmWB and EGWB phytoplasmas within 16SrIX‐C (rpIX‐C) and 16SrIX‐B (rpIX‐B) subgroups, respectively.
Contrasting lineage‐specific patterns conceal community phylogenetic structure in larger clades
Authors: Elliott Tammy L. , Waterway Marcia J. , Davies T. Jonathan 
Published: November 2015

AbstractQuestionCommunity phylogenetic approaches can provide information on the ecological forces structuring plant community composition. For example, assuming evolutionary conservatism of ecological traits, environmental filtering has been suggested to result in phylogenetic clustering, whereas competition has been suggested to lead to phylogenetic over‐dispersion. However, current approaches report aggregate community‐wide metrics and typically assume that all lineages respond similarly. Here, we question this assumption and evaluate evidence for lineage‐specific patterns of co‐occurrence.LocationEastern Canadian subarctic.MethodsWe use a novel individual‐based, neighbourhood approach to evaluate lineage‐specific co‐occurrence patterns among 35 focal species of Cyperaceae (sedges). Cyperaceae is a species‐rich clade, with many species sharing similar niche preferences and environmental tolerances, making this a model clade for evaluating interspecific interaction strengths.ResultsWe reveal striking differences in co‐occurrence patterns between clades. Within the Cyperaceae, the two species of the genus Trichophorum tended to cluster with each other, whereas species within Eriophorum co‐occurred more often with less closely related neighbours. These contrasting patterns repeated themselves within Carex, with species in the Core Carex clade more often co‐occurring with close relatives, while phylogenetic over‐dispersion was more prominent in the Vignea clade. As a consequence of these opposing lineage‐specific relationships, the overall phylogenetic structure of sedge communities appears random.ConclusionsWe show opposing lineage‐specific patterns in phylogenetic structure that are obscured when species are aggregated into larger clades. Our results reveal cryptic complexities in plant community assembly across taxonomic scales, and indicate that different plant lineages may vary in their response to community‐level processes. We suggest that the processes underlying community composition can be better understood by using alternative sampling and analytical approaches combined with thoughtfully‐created null models.
Bringing CLARITY to the human brain: visualization of Lewy pathology in three dimensions
Authors: Liu A. K. L. , Hurry M. E. D. , Ng O.T. W. , DeFelice J. , Lai H. M. , Pearce R. K. B. , Wong G. T‐C. , Chang R. C‐C. , Gentleman S. M. 
Published: November 2015

AimsCLARITY is a novel technique which enables three‐dimensional visualization of immunostained tissue for the study of circuitry and spatial interactions between cells and molecules in the brain. In this study, we aimed to compare methodological differences in the application of CLARITY between rodent and large human post mortem brain samples. In addition, we aimed to investigate if this technique could be used to visualize Lewy pathology in a post mortem Parkinson's brain.MethodsRodent and human brain samples were clarified and immunostained using the passive version of the CLARITY technique. Samples were then immersed in different refractive index matching media before mounting and visualizing under a confocal microscope.ResultsWe found that tissue clearing speed using passive CLARITY differs according to species (human vs. rodents), brain region and degree of fixation (fresh vs. formalin‐fixed tissues). Furthermore, there were advantages to using specific refractive index matching media. We have applied this technique and have successfully visualized Lewy body inclusions in three dimensions within the nucleus basalis of Meynert, and the spatial relationship between monoaminergic fibres and Lewy pathologies among nigrostriatal fibres in the midbrain without the need for physical serial sectioning of brain tissue.ConclusionsThe effective use of CLARITY on large samples of human tissue opens up many potential avenues for detailed pathological and morphological studies.
Drought × CO2interactions in trees: a test of the low‐intercellularCO2concentration (Ci) mechanism
Authors: Kelly Jeff W. G. , Duursma Remko A. , Atwell Brian J. , Tissue David T. , Medlyn Belinda E. 
Published: November 2015

SummaryModels of tree responses to climate typically project that elevated atmosphericCO2concentration (eCa) will reduce drought impacts on forests. We tested one of the mechanisms underlying this interaction, the ‘lowCieffect’, in which stomatal closure in drought conditions reduces the intercellularCO2concentration (Ci), resulting in a larger relative enhancement of photosynthesis witheCa, and, consequently, a larger relative biomass response.We grew twoEucalyptusspecies of contrasting drought tolerance at ambient and elevatedCafor 6–9 months in large pots maintained at 50% (drought) and 100% field capacity.Droughted plants did not have significantly lowerCithan well‐watered plants, which we attributed to long‐term changes in leaf area. Hence, there should not have been an interaction between eCaand water availability on biomass, and we did not detect one. The xeric species did have higherCithan the mesic species, indicating lower water‐use efficiency, but both species exhibited similar responses of photosynthesis and biomass toeCa, owing to compensatory differences in the photosynthetic response toCi.Our results demonstrate that long‐term acclimation to drought, and coordination among species traits may be important for predicting plant responses toeCaunder low water availability.
Aquaporin8 regulates cellular development and reactive oxygen species production, a critical component of virulence in Botrytis cinerea
Authors: An Bang , Li Boqiang , Li Hua , Zhang Zhanquan , Qin Guozheng , Tian Shiping 
Published: November 2015

Summary

Aquaporins (AQPs) are ubiquitous in nearly all organisms, mediating selective and rapid flux of water across biological membranes. The role of AQPs in phytopathogenic fungi is poorly understood.

Orthologs of AQP genes in Botrytis cinerea were identified and knocked out. The effects of AQPs on hyphal growth and conidiation, formation of infection structures and virulence on plant hosts were examined. The role of AQP8 in reactive oxygen species (ROS) production, distribution and transport were further determined.

Among eight AQPs, only AQP8 was essential for the ability of B. cinerea to infect plants. AQP8 was demonstrated to be an intrinsic plasma membrane protein, which may function as a channel and mediate hydrogen peroxide uptake. Deletion of AQP8 in B. cinerea completely inhibited the development of conidia and infection structures, and significantly affected noxR expression. Further observations revealed that both AQP8 and noxR impacted ROS distribution in the hyphal tips of B. cinerea. Moreover, AQP8 affected the expression of a mitochondrial protein, NQO1. A knockout mutant of NQO1 was observed to display reduced virulence.

These data lead to a better understanding of the important role of AQP8 in the development and pathogenesis of plant pathogens.