bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sodium transport through the cerebral sodium–glucose transporter exacerbates neuron damage during cerebral ischaemia
Authors: Yamazaki Yui , Harada Shinichi , Wada Tetsuyuki , Yoshida Shigeru , Tokuyama Shogo 
Published: May 2016

Abstract

Objectives
We recently demonstrated that the cerebral sodium-glucose transporter (SGLT) is involved in postischaemic hyperglycaemia-induced exacerbation of cerebral ischaemia. However, the associated SGLT-mediated mechanisms remain unclear. Thus, we examined the involvement of cerebral SGLT-induced excessive sodium ion influx in the development of cerebral ischaemic neuronal damage.

Methods
[Na+]i was estimated according to sodium-binding benzofuran isophthalate fluorescence. In the in vitro study, primary cortical neurons were prepared from fetuses of ddY mice. Primary cortical neurons were cultured for 5 days before each treatment with reagents, and these survival rates were assessed using biochemical assays. In in vivo study, a mouse model of focal ischaemia was generated using middle cerebral artery occlusion (MCAO).

Key findings
In these experiments, treatment with high concentrations of glucose induced increment in [Na+]i, and this phenomenon was suppressed by the SGLT-specific inhibitor phlorizin. SGLT-specific sodium ion influx was induced using a-methyl-D-glucopyranoside (a-MG) treatments, which led to significant concentration-dependent declines in neuronal survival rates and exacerbated hydrogen peroxide-induced neuronal cell death. Moreover, phlorizin ameliorated these effects. Finally, intracerebroventricular administration of a-MG exacerbated the development of neuronal damage induced by MCAO, and these effects were ameliorated by the administration of phlorizin.

Conclusions
Hence, excessive influx of sodium ions into neuronal cells through cerebral SGLT may exacerbate the development of cerebral ischaemic neuronal damage.
Clinical response of masitinib mesylate in the treatment of canine macroscopic mast cell tumours
Authors: Grant J. , North S. , Lanore D. 
Published: May 2016

OBJECTIVESTo retrospectively evaluate the clinical response and toxicity associated with masitinib mesylate (Masivet®) treatment of macroscopic mast cell tumours in the dog.METHODSRetrospective review of medical records of 39 dogs that had undergone treatment with masitinib for macroscopic mast cell tumours. Patient signalment, tumour location, tumour grade, tumour stage, previous treatments, concurrent medications, dose of masitinib, side effects, response, time to tumour progression, survival time and cause of death were documented. Response was assessed according to RECIST criteria.RESULTSClinical response was observed in 32 (82·1%) dogs receiving masitinib, with 15 dogs (38·5%) exhibiting a complete response and 17 dogs (43·6%) achieving a partial response. The median time to progression was 79 days (range: 14 to 667 days). Adverse effects were seen in 25 dogs (64·1%) with serum alanine aminotransferase elevation (n=9; 23·1%) and vomiting (n=6; 15·4%) being most common. Median survival time following initiation of masitinib was 159 days (range: 14 to 1339).CLINICAL SIGNIFICANCEMasitinib appears to be a well‐tolerated and effective drug against macroscopic mast cell tumours.
Sleep fragmentation alters brain energy metabolism without modifying hippocampal electrophysiological response to novelty exposure
Authors: Baud Maxime O. , Parafita Julia , Nguyen Audrey , Magistretti Pierre J. , Petit Jean‐Marie 
Published: May 2016

SummarySleep is viewed as a fundamental restorative function of the brain, but its specific role in neural energy budget remains poorly understood. Sleep deprivation dampens brain energy metabolism and impairs cognitive functions. Intriguingly, sleep fragmentation, despite normal total sleep duration, has a similar cognitive impact, and in this paper we ask the question of whether it may also impair brain energy metabolism. To this end, we used a recently developed mouse model of 2 weeks of sleep fragmentation and measured 2‐deoxy‐glucose uptake and glycogen, glucose and lactate concentration in different brain regions. In order to homogenize mice behaviour during metabolic measurements, we exposed them to a novel environment for 1 h. Using an intra‐hippocampal electrode, we first showed that hippocampal electroencephalograph (EEG) response to exploration was unaltered by 1 or 14 days of sleep fragmentation. However, after 14 days, sleep fragmented mice exhibited a lower uptake of 2‐deoxy‐glucose in cortex and hippocampus and lower cortical lactate levels than control mice. Our results suggest that long‐term sleep fragmentation impaired brain metabolism to a similar extent as total sleep deprivation without affecting the neuronal responsiveness of hippocampus to a novel environment.
Thinking Is Modulated by Recent Linguistic Experience: Second Language Priming Affects Perceived Event Similarity
Authors: Montero‐Melis Guillermo , Jaeger T. Florian , Bylund Emanuel 
Published: May 2016

AbstractCan recent second language (L2) exposure affect what we judge to be similar events? Using a priming paradigm, we manipulated whether native Swedish adult learners of L2 Spanish were primed to use path or manner during L2 descriptions of scenes depicting caused motion events (encoding phase). Subsequently, participants engaged in a nonverbal task, arranging events on the screen according to similarity (test phase). Path versus manner priming affected how participants judged event similarity during the test phase. The effects we find support the hypotheses that (a) speakers create or select ad hoc conceptual categories that are based on linguistic knowledge to carry out nonverbal tasks, and that (b) short‐term, recent L2 experience can affect this ad hoc process. These findings further suggest that cognition can flexibly draw on linguistic categories that have been implicitly highlighted during recent exposure.Open PracticesThis article has been awarded an Open Data badge. All data are publicly accessible via the Harvard Dataverse athttp://dx.doi.org/10.7910/DVN/QOD8ZU. Learn more about the Open Practices badges from the Center for Open Science:https://osf.io/tvyxz/wiki.
When rumination counts: Perceived social support and heart rate variability in daily life
Authors: Gerteis Ann Kathrin S. , Schwerdtfeger Andreas R. 
Published: May 2016

AbstractRumination and social support could modulate cardiac activity. Although both variables are somehow interrelated, they are often studied independently, and their interplay is seldom considered. We aimed to analyze the interaction of rumination and perceived social support on vagally mediated heart rate variability (HRV) in daily life. The sample consisted of 117 healthy participants (57% female, mean age = 27.9, SD = 5.5 years). Ambulatory HRV (root mean squared successive differences), respiration, body position, and body movements were recorded continuously on three consecutive weekdays. Momentary social, situational, and cognitive‐affective variables (affect, ruminative thoughts, perceived social support) were assessed using a computerized diary. There was a significant interaction between momentary rumination and perceived social support on ambulatory HRV: When participants were involved in social interactions with low social support, concurrent rumination was associated with attenuated HRV. However, when rumination was accompanied by a strong sense of support, HRV significantly increased. The quality of social interactions and rumination seem to interact in daily life to predict cardiac autonomic control. The results stress the necessity to consider the interplay of psychological and social factors in order to evaluate beneficial or adverse effects on cardiac health.
Tax Revenue Effects of Sectoral Growth and Public Expenditure in Uganda
Authors: Mawejje Joseph , Francis Munyambonera Ezra 
Published: May 2016

AbstractThis paper contributes to a growing strand of literature on the determinants of tax revenue performance in developing countries, particularly in Sub‐Saharan Africa. More specifically we estimate the tax elasticities of sectoral output growth and public expenditure. The unique features of this paper are twofold: First, we develop a simple analytical model for tax revenue performance taking into account some structural features pervasive in most developing countries with large informal sectors. Second, we test the model predictions on Ugandan time series data using ARDL bounds testing techniques. Results indicate that dominance of the agricultural and informal sectors pose the largest impediments to tax revenue performance. In addition development expenditures, trade openness, and industrial sector growth are positively associated with tax revenue performance. We propose policies to support the development of value added linkages between agricultural and industrial sectors while emphasizing the need to unlock the potentially large contributions of the informal sector with a view of widening the tax base.
Genetic variants associated with physical and mental characteristics of the elite athletes in the Polish population
Authors: Peplonska B. , Adamczyk J. G. , Siewierski M. , Safranow K. , Maruszak A. , Sozanski H. , Gajewski A. K. , Zekanowski C. 
Published: May 2016

The aim of the study was to assess whether selected genetic variants are associated with elite athlete performance in a group of 413 elite athletes and 451 sedentary controls. Polymorphisms in ACE, ACTN3, AGT, NRF‐2, PGC1A, PPARG, and TFAM implicated in physical performance traits were analyzed. Additionally, polymorphisms in CHRNB3 and FAAH coding for proteins modulating activity of brain's emotion centers were included. The results of univariate analyses indicated that the elite athletic performance is associated with four polymorphisms: ACE (rs4341, P = 0.0095), NRF‐2 (rs12594956, P = 0.011), TFAM (rs2306604, P = 0.049), and FAAH (rs324420, P = 0.0041). The multivariate analysis adjusted for age and gender confirmed this association. The higher number of ACE D alleles (P = 0.0021) and the presence of NRF‐2 rs12594956 A allele (P = 0.0067) are positive predictors, whereas TFAM rs2306604 GG genotype (P = 0.031) and FAAH rs324420 AA genotype (P = 0.0084) negatively affect the elite athletic performance. The CHRNB3 variant (rs4950, G allele) is significantly more frequent in the endurance athletes compared with the power ones (P = 0.025). Multivariate analysis demonstrated that the presence of rs4950 G allele contributes to endurance performance (P = 0.0047). Our results suggest that genetic inheritance of psychological traits should be taken into consideration while trying to decipher a genetic profile of top athletic performance.
Immortalization and characterization of a new canine mammary tumour cell line FR37‐CMT
Authors: Raposo L. R. , Roma‐Rodrigues C. , Faísca P. , Alves M. , Henriques J. , Carvalheiro M. C. , Corvo M. L. , Baptista P. V. , Pombeiro A. J. , Fernandes A. R. 
Published: May 2016

AbstractHere we describe the establishment of a new canine mammary tumour (CMT) cell line, FR37‐CMT that does not show dependence on female hormonal signaling to induce tumour xenografts in NOD‐SCID mice. FR37‐CMT cell line has a stellate or fusiform shape, displays the ability to reorganize the collagen matrix, expresses vimentin, CD44 and shows the loss of E‐cadherin which is considered a fundamental event in epithelial to mesenchymal transition (EMT). The up‐regulation of ZEB1, the detection of phosphorylated ERK1/2 and the downregulation of DICER1 and miR‐200c are also in accordance with the mesenchymal characteristics of FR37‐CMT cell line. FR37‐CMT shows a higher resistance to cisplatin (IC50>50 µM) and to doxorubicin (IC50>5.3 µM) compared with other CMT cell lines. These results support the use of FR37‐CMT as a new CMT model that may assist the understanding of the molecular mechanisms underlying EMT, CMT drug resistance, fostering the development of novel therapies targeting CMT.
Contextualising a pedagogical model for English‐language education in Hong Kong
Authors: CHAN JIM Y. H. 
Published: May 2016

ABSTRACTA major controversy in the fields of World Englishes (WE) and English as a lingua franca (ELF) has been the application of exonormative Inner Circle norms to ELT classrooms in diverse multilingual societies. This article seeks to examine the suitability of adopting a WE and/or an ELF‐oriented pedagogical model, as well as the corresponding research findings, in Hong Kong's ELT classroom. More specifically, the study investigated the use of English by the local professionals and, furthermore, evaluated the comparability of Hong Kong's sociolinguistic reality to typical WE and ELF contexts via a structured questionnaire survey and semi‐structured interviews.
A Multinational, Preregistered Cohort Study of β-Lactam/β-Lactamase Inhibitor Combinations for Treatment of Bloodstream Infections Due to Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae
Authors: Gutiérrez-Gutiérrez Belén , Pérez-Galera Salvador , Salamanca Elena , de Cueto Marina , Calbo Esther , Almirante Benito , Viale Pierluigi , Oliver Antonio , Pintado Vicente , Gasch Oriol , Martínez-Martínez Luis , Pitout Johann , Akova Murat , Peña Carmen , Molina José , Hernández Alicia , Venditti Mario , Prim Nuria , Origüen Julia , Bou German , Tacconelli Evelina , Tumbarello Mario , Hamprecht Axel , Giamarellou Helen , Almela Manel , Pérez Federico , Schwaber Mitchell J. , Bermejo Joaquín , Lowman Warren , Hsueh Po-Ren , Mora-Rillo Marta , Natera Clara , Souli Maria , Bonomo Robert A. , Carmeli Yehuda , Paterson David L. , Pascual Alvaro , Rodríguez-Baño Jesús 
Published: May 2016

ABSTRACT

The spread of extended-spectrum-β-lactamase (ESBL)-producing
Enterobacteriaceae
(ESBL-E) is leading to increased carbapenem consumption. Alternatives to carbapenems need to be investigated. We investigated whether β-lactam/β-lactamase inhibitor (BLBLI) combinations are as effective as carbapenems in the treatment of bloodstream infections (BSI) due to ESBL-E. A multinational, retrospective cohort study was performed. Patients with monomicrobial BSI due to ESBL-E were studied; specific criteria were applied for inclusion of patients in the empirical-therapy (ET) cohort (ETC; 365 patients), targeted-therapy (TT) cohort (TTC; 601 patients), and global cohort (GC; 627 patients). The main outcome variables were cure/improvement rate at day 14 and all-cause 30-day mortality. Multivariate analysis, propensity scores (PS), and sensitivity analyses were used to control for confounding. The cure/improvement rates with BLBLIs and carbapenems were 80.0% and 78.9% in the ETC and 90.2% and 85.5% in the TTC, respectively. The 30-day mortality rates were 17.6% and 20% in the ETC and 9.8% and 13.9% in the TTC, respectively. The adjusted odds ratio (OR) (95% confidence interval [CI]) values for cure/improvement rate with ET with BLBLIs were 1.37 (0.69 to 2.76); for TT, they were 1.61 (0.58 to 4.86). Regarding 30-day mortality, the adjusted OR (95% CI) values were 0.55 (0.25 to 1.18) for ET and 0.59 (0.19 to 1.71) for TT. The results were consistent in all subgroups studied, in a stratified analysis according to quartiles of PS, in PS-matched cases, and in the GC. BLBLIs, if active
in vitro
, appear to be as effective as carbapenems for ET and TT of BSI due to ESLB-E regardless of the source and specific species. These data may help to avoid the overuse of carbapenems. (This study has been registered at ClinicalTrials.gov under registration no. NCT01764490.)
Characteristics and Outcomes of Complicated Intra-abdominal Infections Involving Pseudomonas aeruginosa from a Randomized, Double-Blind, Phase 3 Ceftolozane-Tazobactam Study
Authors: Miller Benjamin , Popejoy Myra W. , Hershberger Ellie , Steenbergen Judith N. , Alverdy John 
Published: May 2016

ABSTRACT

Ceftolozane-tazobactam is active against Gram-negative pathogens, including multidrug-resistant
Pseudomonas aeruginosa
. In a subgroup analysis of patients with complicated intra-abdominal infections (cIAIs) involving
P. aeruginosa
from a phase 3 program, ceftolozane-tazobactam demonstrated potent
in vitro
activity against
P. aeruginosa
. Clinical cure in the microbiologically evaluable population was 100% (26/26) for ceftolozane-tazobactam plus metronidazole and 93.1% (27/29) for meropenem. These findings support the use of ceftolozane-tazobactam in the management of cIAI when
P. aeruginosa
is suspected or confirmed. (This study has been registered at ClinicalTrials.gov under registration no. NCT01445665 and NCT01445678.)
Antifungal Mechanism of Action of Lactoferrin: Identification of H
+
-ATPase (P
3A
-Type) as a New Apoptotic-Cell Membrane Receptor
Authors: Andrés María T. , Acosta-Zaldívar Maikel , Fierro José F. 
Published: May 2016

ABSTRACT

Human lactoferrin (hLf) is a protein of the innate immune system which induces an apoptotic-like process in yeast. Determination of the susceptibility to lactoferrin of several yeast species under different metabolic conditions, respiratory activity, cytoplasmic ATP levels, and external medium acidification mediated by glucose assays suggested plasma membrane Pma1p (P
3A
-type ATPase) as the hLf molecular target. The inhibition of plasma membrane ATPase activity by hLf and the identification of Pma1p as the hLf-binding membrane protein confirmed the previous physiological evidence. Consistent with this, cytoplasmic ATP levels progressively increased in hLf-treated
Candida albicans
cells. However, oligomycin, a specific inhibitor of the mitochondrial F-type ATPase proton pump (mtATPase), abrogated the antifungal activity of hLf, indicating a crucial role for mtATPase in the apoptotic process. We suggest that lactoferrin targeted plasma membrane Pma1p H
+
-ATPase, perturbing the cytoplasmic ion homeostasis (i.e., cytoplasmic H
+
accumulation and subsequent K
+
efflux) and inducing a lethal mitochondrial dysfunction. This initial event involved a normal mitochondrial ATP synthase activity responsible for both the ATP increment and subsequent hypothetical mitochondrial proton flooding process. We conclude that human lactoferrin inhibited Pma1p H
+
-ATPase, inducing an apoptotic-like process in metabolically active yeast. Involvement of mitochondrial H
+
-ATPase (nonreverted) was essential for the progress of this programmed cell death in which the ionic homeostasis perturbation seems to precede classical nonionic apoptotic events.
Identification, Characterization, and Application of the Replicon Region of the Halophilic Temperate Sphaerolipovirus SNJ1
Authors: Wang Yuchen , Sima Linshan , Lv Jie , Huang Suiyuan , Liu Ying , Wang Jiao , Krupovic Mart , Chen Xiangdong 
Published: May 2016

ABSTRACT

The temperate haloarchaeal virus SNJ1 displays lytic and lysogenic life cycles. During the lysogenic cycle, the virus resides in its host,
Natrinema
sp. strain J7-1, in the form of an extrachromosomal circular plasmid, pHH205. In this study, a 3.9-kb region containing seven predicted genes organized in two operons was identified as the minimal replicon of SNJ1. Only RepA, encoded by open reading frame 11-12 (ORF11-12), was found to be essential for replication, and its expression increased during the lytic cycle. Sequence analysis suggested that RepA is a distant homolog of HUH endonucleases, a superfamily that includes rolling-circle replication initiation proteins from various viruses and plasmids. In addition to RepA, two genetic elements located within both termini of the 3.9-kb replicon were also required for SNJ1 replication. SNJ1 genome and SNJ1 replicon-based shuttle vectors were present at 1 to 3 copies per chromosome. However, the deletion of ORF4 significantly increased the SNJ1 copy number, suggesting that the product of ORF4 is a negative regulator of SNJ1 abundance. Shuttle vectors based on the SNJ1 replicon were constructed and validated for stable expression of heterologous proteins, both in J7 derivatives and in
Natrinema
pallidum
JCM 8980
T
, suggesting their broad applicability as genetic tools for
Natrinema
species.

IMPORTANCE
Archaeal viruses exhibit striking morphological diversity and unique gene content. In this study, the minimal replicon of the temperate haloarchaeal virus SNJ1 was identified. A number of ORFs and genetic elements controlling virus genome replication, maintenance, and copy number were characterized. In addition, based on the replicon, a novel expression shuttle vector has been constructed and validated for protein expression and purification in
Natrinema
sp. CJ7 and
Natrinema pallidum
JCM 8980
T
. This study not only provided mechanistic and functional insights into SNJ1 replication but also led to the development of useful genetic tools to investigate SNJ1 and other viruses infecting
Natrinema
species as well as their hosts.
Biosynthetic Genes for the Tetrodecamycin Antibiotics
Authors: Gverzdys Tomas , Nodwell Justin R. 
Published: May 2016

ABSTRACT

We recently described 13-deoxytetrodecamycin, a new member of the tetrodecamycin family of antibiotics. A defining feature of these molecules is the presence of a five-membered lactone called a tetronate ring. By sequencing the genome of a producer strain,
Streptomyces
sp. strain WAC04657, and searching for a gene previously implicated in tetronate ring formation, we identified the biosynthetic genes responsible for producing 13-deoxytetrodecamycin (the
ted
genes). Using the
ted
cluster in WAC04657 as a reference, we found related clusters in three other organisms:
Streptomyces atroolivaceus
ATCC 19725,
Streptomyces globisporus
NRRL B-2293, and
Streptomyces
sp. strain LaPpAH-202. Comparing the four clusters allowed us to identify the cluster boundaries. Genetic manipulation of the cluster confirmed the involvement of the
ted
genes in 13-deoxytetrodecamycin biosynthesis and revealed several additional molecules produced through the
ted
biosynthetic pathway, including tetrodecamycin, dihydrotetrodecamycin, and another, W5.9, a novel molecule. Comparison of the bioactivities of these four molecules suggests that they may act through the covalent modification of their target(s).

IMPORTANCE
The tetrodecamycins are a distinct subgroup of the tetronate family of secondary metabolites. Little is known about their biosynthesis or mechanisms of action, making them an attractive subject for investigation. In this paper we present the biosynthetic gene cluster for 13-deoxytetrodecamycin in
Streptomyces
sp. strain WAC04657. We identify related clusters in several other organisms and show that they produce related molecules.