bluuebunny/crossref_metadata_2025_split huggingface dataset:
Melatonin attenuates D‐galactose‐induced memory impairment, neuroinflammation and neurodegeneration via RAGE/NF‐KB/JNK signaling pathway in aging mouse model
Authors: Ali Tahir , Badshah Haroon , Kim Tae Hyun , Kim Myeong Ok 
Published: November 2014

AbstractMelatonin acts as a pleiotropic agent in various age‐related neurodegenerative diseases. In this study, we examined the underlying neuroprotective mechanism of melatonin against D‐galactose‐induced memory and synaptic dysfunction, elevated reactive oxygen species (ROS), neuroinflammation and neurodegeneration. D‐galactose was administered (100 mg/kg intraperitoneally (i.p.)) for 60 days. After 30 days of D‐galactose administration, vehicle (same volume) or melatonin (10 mg/kg, i.p.) was administered for 30 days. Our behavioral (Morris water maze and Y‐maze test) results revealed that chronic melatonin treatment alleviated D‐galactose‐induced memory impairment. Additionally, melatonin treatment reversed D‐galactose‐induced synaptic disorder via increasing the level of memory‐related pre‐and postsynaptic protein markers. We also determined that melatonin enhances memory function in the D‐galactose‐treated mice possibly via reduction of elevated ROS and receptor for advanced glycation end products (RAGE). Furthermore, Western blot and morphological results showed that melatonin treatment significantly reduced D‐galactose‐induced neuroinflammation through inhibition of microgliosis (Iba‐1) and astrocytosis (GFAP), and downregulating other inflammatory mediators such as p‐IKKβ, p‐NF‐KB65, COX2, NOS2, IL‐1β, and TNFα. Moreover, melatonin lowered the oxidative stress kinase p‐JNK which suppressed various apoptotic markers, that is, cytochrome C, caspase‐9, caspase‐3 and PARP‐1, and prevent neurodegeneration. Hence, melatonin attenuated the D‐galactose‐induced memory impairment, neuroinflammation and neurodegeneration possibly through RAGE/NF‐KB/JNK pathway. Taken together, our data suggest that melatonin could be a promising, safe and endogenous compatible antioxidant candidate for age‐related neurodegenerative diseases such as Alzheimer's disease (AD).
Sexual Functioning in Women After Surgical Treatment for Endometrial Cancer: A Prospective Controlled Study
Authors: Aerts Leen , Enzlin Paul , Verhaeghe Johan , Poppe Willy , Vergote Ignace , Amant Frédéric 
Published: November 2014

ABSTRACT

Introduction
Endometrial cancer (EC) can affect sexual functioning based on anatomical, physiological, psychological, and relational mechanisms.

Aim
The aim of this study was to prospectively investigate sexual adjustment of women with EC during a follow-up period of 2 years after surgical treatment and to compare the results with women who underwent a hysterectomy for a benign gynecological condition and healthy control women.

Methods/Main Outcome Measures
In this prospective controlled study, participants completed the Short Sexual Functioning Scale, Specific Sexual Problems Questionnaire, Beck Depression Inventory Scale, World Health Organization-5 Well-being Scale, and Dyadic Adjustment Scale to assess various aspects of sexual and psychosocial functioning before undergoing a hysterectomy and 6 months, 1 year, and 2 years after surgery.

Results
Eighty-four women with EC, 84 women with a benign gynecological condition, and 84 healthy controls completed the survey. In EC survivors, no differences were found in sexual functioning during prospective analyses. In comparison with women with a benign gynecological condition, significantly more EC patients reported entry dyspareunia 1 year after surgical treatment. Moreover, compared with healthy women, pre- and postoperatively, significantly more EC patients reported sexual dysfunctions, including sexual desire dysfunction, arousal dysfunction, entry dyspareunia, and a reduced intensity of orgasm. Furthermore, compared with healthy controls, EC patients reported significantly lower overall well-being 1 year after surgical treatment. Nevertheless, consensus in the partner relationship was significantly higher in EC patients compared with healthy controls. Moreover, before treatment, quality of partner relationship was negatively associated with sexual arousal dysfunction and orgasm dysfunction.

Conclusions
In EC patients, no differences were found in sexual functioning when prospectively comparing the situation before surgery with the situation after surgery. However, when compared with healthy controls, EC patients are at high risk for sexual dysfunctions, both before and after surgical treatment.
Incidence of virological failure and emergence of resistance with twice‐daily vs every 8‐h administration of telaprevir in the OPTIMIZE study
Authors: Dierynck I. , Ghys A. , Witek J. , Luo D. , Janssen K. , Daems B. , Picchio G. , Buti M. , De Meyer S. 
Published: November 2014

SummaryThe OPTIMIZE study demonstrated noninferior efficacy between telaprevir (TVR) twice daily (bid) vs every 8‐h (q8h) administration. This analysis compared the selective pressure of both dosing regimens by characterisation of the hepatitis C virus (HCV) variants emerging in genotype 1 (G1) HCV‐infected patients who did not achieve sustained virological response (SVR). HCV NS3•4A population sequencing was performed at baseline and time of failure (viral breakthrough, stopping rule or relapse). TVR‐resistant variants were classified by fold change in inhibitory concentration (IC50). Baseline TVR‐resistance was low (<5%) and did not preclude achieving SVR in either arm. The proportion of patients with TVR‐resistant variants at time of failure was similar in the bid (15%) and q8h (17%) dosing arms. The majority of variants and virological failures occurred in G1a patients, and mutations V36M, R155K and R155T (G1a), and V36A, T54A and A156S (G1b) were significantly enriched in both treatment arms. The number and type of emerging TVR‐resistant variants in non‐SVR patients were comparable between treatment arms and were consistent with previous observations. No differences in viral resistance profiles were observed between TVR‐based treatment arms in non‐SVR patients, indicating a similar selective pressure of TVR bid and q8h dosing.
Impacts of selective logging on inbreeding and gene flow in two Amazonian timber species with contrasting ecological and reproductive characteristics
Authors: Vinson C. C. , Kanashiro M. , Harris S. A. , Boshier D. H. 
Published: November 2014

AbstractSelective logging in Brazil allows for the removal of up to 90% of trees above 50 cm diameter of a given timber species, independent of a species’ life history characteristics or how quickly it will recover. The genetic and demographic effects of selective logging on two Amazonian timber species (Dipteryx odorata Leguminosae, Jacaranda copaia Bignoniaceae) with contrasting ecological and reproductive characteristics were assessed in the same forest. Genetic diversity and gene flow were characterized by genotyping adults and seed sampled before and after logging, using hypervariable microsatellite markers. Overall, there were no short‐term genetic impacts on the J. copaia population, with commercial application of current Brazilian forest management regulations. In contrast, for D. Odorata, selective logging showed a range of genetic impacts, with a 10% loss of alleles, and reductions in siring by pollen from trees within the 546‐ha study area (23–11%) and in the number of pollen donors per progeny array (2.8–1.6), illustrating the importance of the surrounding landscape. Asynchrony in flowering between D. odorata trees led to trees with no breeding partners, which could limit the species reproduction and regeneration under current regulations. The results are summarized with other published studies from the same site and the implications for forest management discussed. The different types and levels of impacts associated with each species support the idea that ecological and genetic information by species, ecological guild or reproductive group is essential in helping to derive sustainable logging guidelines for tropical forests.
The atypical response regulator HP1021 controls formation of the Helicobacter pylori replication initiation complex
Authors: Donczew Rafał , Makowski Łukasz , Jaworski Paweł , Bezulska Martyna , Nowaczyk Małgorzata , Zakrzewska‐Czerwińska Jolanta , Zawilak‐Pawlik Anna 
Published: November 2014

SummaryThe replication of a bacterial chromosome is initiated by the DnaA protein, which binds to the specific chromosomal region oriC and unwinds duplex DNA within the DNA‐unwinding element (DUE). The initiation is tightly regulated by many factors, which control either DnaA or oriC activity and ensure that the chromosome is duplicated only when the conditions favor the survival of daughter cells. The factors controlling oriC activity often belong to the protein families of two‐component systems. Here, we found that Helicobacter pylori oriC activity is controlled by HP1021, a member of the atypical response regulator family. HP1021 protein specifically interacts with H. pylori oriC at HP1021 boxes (5′‐TGTT[TA]C[TA]‐3′), which overlap with three modules important for oriC function: DnaA boxes, the hypersensitivity (hs) region and the DUE. Consequently, HP1021 binding to oriC precludes DnaA‐oriC interactions and inhibits DNA unwinding at the DUE. Thus, HP1021 constitutes a negative regulator of the H. pylori orisome assembly in vitro. Furthermore, HP1021 boxes were found upstream of at least 70 genes, including those encoding CagA and Fur proteins. We postulate that HP1021 might coordinate chromosome replication, and thus bacterial growth, with other cellular processes and conditions in the human stomach.
Crystal structure of Bacillus anthracis virulence regulator AtxA and effects of phosphorylated histidines on multimerization and activity
Authors: Hammerstrom Troy G. , Horton Lori B. , Swick Michelle C. , Joachimiak Andrzej , Osipiuk Jerzy , Koehler Theresa M. 
Published: November 2014

SummaryThe Bacillus anthracis virulence regulator AtxA controls transcription of the anthrax toxin genes and capsule biosynthetic operon. AtxA activity is elevated during growth in media containing glucose and CO2/bicarbonate, and there is a positive correlation between the CO2/bicarbonate signal, AtxA activity and homomultimerization. AtxA activity is also affected by phosphorylation at specific histidines. We show that AtxA crystallizes as a dimer. Distinct folds associated with predicted DNA‐binding domains (HTH1 and HTH2) and phosphoenolpyruvate: carbohydrate phosphotransferase system‐regulated domains (PRD1 and PRD2) are apparent. We tested AtxA variants containing single and double phosphomimetic (His→Asp) and phosphoablative (His→Ala) amino acid changes for activity in B. anthracis cultures and for protein–protein interactions in cell lysates. Reduced activity of AtxA H199A, lack of multimerization and activity of AtxAH379D variants, and predicted structural changes associated with phosphorylation support a model for control of AtxA function. We propose that (i) in the AtxA dimer, phosphorylation of H199 in PRD1 affects HTH2 positioning, influencing DNA‐binding; and (ii) phosphorylation of H379 in PRD2 disrupts dimer formation. The AtxA structure is the first reported high‐resolution full‐length structure of a PRD‐containing regulator, and can serve as a model for proteins of this family, especially those that link virulence to bacterial metabolism.
Membrane‐binding mechanism of a bacterial phospholipid N‐methyltransferase
Authors: Danne Linna , Aktas Meriyem , Gleichenhagen Jan , Grund Nadine , Wagner Dominic , Schwalbe Harald , Hoffknecht Barbara , Metzler‐Nolte Nils , Narberhaus Franz 
Published: November 2014

SummaryThe membrane lipid phosphatidylcholine (PC) is crucial for stress adaptation and virulence of the plant pathogen Agrobacterium tumefaciens. The phospholipid N‐methyltransferase PmtA catalyzes three successive methylations of phosphatidylethanolamine to yield PC. Here, we asked how PmtA is recruited to its site of action, the inner leaflet of the membrane. We found that the enzyme attaches to the membrane via electrostatic interactions with anionic lipids, which do not serve as substrate for PmtA. Increasing PC concentrations trigger membrane dissociation suggesting that membrane binding of PmtA is negatively regulated by its end product PC. Two predicted alpha‐helical regions (αA and αF) contribute to membrane binding of PmtA. The N‐terminal helix αA binds anionic lipids in vitro with higher affinity than the central helix αF. The latter undergoes a structural transition from disordered to α‐helical conformation in the presence of anionic lipids. The basic amino acids R8 and K12 and the hydrophobic amino acid F19 are critical for membrane binding by αA as well as for activity of full‐length PmtA. We conclude that a combination of electrostatic and hydrophobic forces is responsible for membrane association of the phospholipid‐modifying enzyme.
Effect of ocular transverse chromatic aberration on detection acuity for peripheral vision
Authors: Cheney Frank , Thibos Larry , Bradley Arthur 
Published: November 2014

AbstractPurposeWe examined the effect of transverse chromatic aberration (TCA) on detection acuity for white‐light interference fringes seen in Maxwellian view at various orientations and locations in the visual field.MethodsA circular patch (3.5° diameter, 3.2 log Trolands) of nominally high‐contrast fringes was produced on the retina by a commercial instrument (the Lotmar Visometer, Haag Streit) mounted on a gimbal for controlled positioning of the stimulus in the visual field from 0° to 35° eccentricity.ResultsDetection acuity for white light fringes for all meridians and eccentricities ≥15° was maximum when fringes were oriented parallel to the visual meridian line. This meridional effect disappeared when a narrow‐band filter was used to eliminate TCA. The meridional effect also disappeared when the interferometric stimulator was displaced laterally to align the instrument with the eye's local achromatic axis.ConclusionsModelling confirmed that TCA is the major factor responsible for white‐light meridional bias, with minor contribution arising from higher‐order monochromatic aberrations and neural factors.
Petunia × hybrida floral scent production is negatively affected by high‐temperature growth conditions
Authors: CNA'ANI ALON , MÜHLEMANN JOELLE K. , RAVID JASMIN , MASCI TANIA , KLEMPIEN ANTJE , NGUYEN THUONG T. H. , DUDAREVA NATALIA , PICHERSKY ERAN , VAINSTEIN ALEXANDER 
Published: November 2014

AbstractIncreasing temperatures due to changing global climate are interfering with plant–pollinator mutualism, an interaction facilitated mainly by floral colour and scent. Gas chromatography–mass spectroscopy analyses revealed that increasing ambient temperature leads to a decrease in phenylpropanoid‐based floral scent production in two Petunia × hybrida varieties, P720 and Blue Spark, acclimated at 22/16 or 28/22 °C (day/night). This decrease could be attributed to down‐regulation of scent‐related structural gene expression from both phenylpropanoid and shikimate pathways, and up‐regulation of a negative regulator of scent production, emission of benzenoids V (EOBV). To test whether the negative effect of increased temperature on scent production can be reduced in flowers with enhanced metabolic flow in the phenylpropanoid pathway, we analysed floral volatile production by transgenic ‘Blue Spark’ plants overexpressing CaMV 35S‐driven Arabidopsis thaliana production of anthocyanin pigments 1 (PAP1) under elevated versus standard temperature conditions. Flowers of 35S:PAP1 transgenic plants produced the same or even higher levels of volatiles when exposed to a long‐term high‐temperature regime. This phenotype was also evident when analysing relevant gene expression as inferred from sequencing the transcriptome of 35S:PAP1 transgenic flowers under the two temperature regimes. Thus, up‐regulation of transcription might negate the adverse effects of temperature on scent production.
Heritability and molecular genetic basis of antisaccade eye tracking error rate: A genome‐wide association study
Authors: Vaidyanathan Uma , Malone Stephen M. , Donnelly Jennifer M. , Hammer Micah A. , Miller Michael B. , McGue Matt , Iacono William G. 
Published: November 2014

AbstractAntisaccade deficits reflect abnormalities in executive function linked to various disorders including schizophrenia, externalizing psychopathology, and neurological conditions. We examined the genetic bases of antisaccade error in a sample of community‐based twins and parents (N = 4,469). Biometric models showed that about half of the variance in the antisaccade response was due to genetic factors and half due to nonshared environmental factors. Molecular genetic analyses supported these results, showing that the heritability accounted for by common molecular genetic variants approximated biometric estimates. Genome‐wide analyses revealed several SNPs as well as two genes—B3GNT7 and NCL—on Chromosome 2 associated with antisaccade error. SNPs and genes hypothesized to be associated with antisaccade error based on prior work, although generating some suggestive findings for MIR137, GRM8, and CACNG2, could not be confirmed.
A case of primary choroidal malignant melanoma in a cat
Authors: Bourguet Aurélie , Piccicuto Virginie , Donzel Elise , Carlus Marine , Chahory Sabine 
Published: November 2014

AbstractThis report describes the clinical presentation, diagnosis, histological lesions, and prognosis of a primary choroidal malignant melanoma in a 15‐year‐old cat. The animal was presented for unilateral blindness. On ocular examination, a raised pigmented mass protruding from the posterior pole into the vitreous body was observed by diffuse transillumination and indirect ophthalmoscopy. Ocular ultrasound and computer tomography (CT) scan confirmed localization of the tumor to the posterior segment. The diagnosis of primary choroidal melanoma was confirmed by histopathology after enucleation. To our knowledge, this is the first reported case of a feline malignant melanoma with a primary choroidal localization without iris involvement.
English in Southeast Asia: Pedagogical and policy implications
Authors: KIRKPATRICK ANDY 
Published: November 2014

ABSTRACTThe roles of English within and between the many of the countries which make up Southeast Asia are increasing, and English is constantly being used and negotiated as a mutual means of communication by Asian multilinguals for whom English is an additional language. It is timely, therefore, to consider ways in which these Englishes have been developing, along with the roles English is currently playing. Areas worthy of investigation include the influence of language contact and the motivations for the presence of non‐standard forms in these new varieties of English. Given the recent research reviewed in this paper, the criteria by which the use of non‐standard forms are classified as characteristic of the particular variety need to be revised. The paper will conclude by considering whether the role of English as a lingua franca in the region has reached its zenith and whether regional language education policy is likely allow the languages of Asia to thrive.
Research on English in Singapore
Authors: LOW EE‐LING 
Published: November 2014

ABSTRACTResearch on English in Singapore has been the topic of many studies from the late 1970s to the present. Past surveys on the topic have tended to focus on the phasing of the study of Singapore English, rather than on the broader issue of English in Singaporeper se. From the late 1990s, we see the birth of a new generation of scholars on Singapore English whose doctoral dissertations have focused on Singapore English, and who have focused on the systematic, features‐based linguistic description of Singapore English as well as the broader consideration of English in Singapore in general. The present paper takes its reference from an up‐to‐date compilation of published works of English in Singapore and doctoral dissertations, and attempts a meta‐analysis via a systematic coding of all the works done. A critical evaluation of what existing research implies about the theoretical modelling of English in Singapore and areas requiring further research will be elucidated in the final section.
English language teaching in the Philippines
Authors: MARTIN ISABEL PEFIANCO 
Published: November 2014

ABSTRACTResearch in world Englishes (WE) and English as a Lingua Franca (ELF) have long been promoting what Pakir describes as ‘common working axioms’ (2009: 228) which uphold the pluricentricity of English: the existence of varieties, the acceptance of language change and adaptation, and the highlighting of discourse strategies. These principles have had profound effects on our understanding of the English language and, consequently, on the teaching of the language. In this paper, I argue that, for all the benefits offered by varieties of English, it might not be appropriate to teach varieties explicitly as a model to non‐native learners of the language. I make this argument with the Philippine education context in mind, and propose a framework for Philippine ELT that recognizes both the identity and communication functions of the language.
English in higher education in Cambodia
Authors: HASHIM AZIRAH , CHEE LEONG YEE , TRA PICH PHEAK 
Published: November 2014

ABSTRACTThis paper discusses a number of key issues in English education and research in Cambodia. Multiple studies on Cambodia often suggest that English is a key component required to transform the standard of life of common Cambodians (Clayton ). To understand the phenomenon of the ever‐increasing demand for English in the country, we conducted a series of semi‐structured interviews with teachers and students followed by a needs analysis of English language learners in a tertiary institution. Our findings suggest that these future employees have a great enthusiasm for learning English mostly mediated by economic imperatives, in a changing world that prioritizes proficiency in the English language. Moreover, it was also found that research in higher education in Cambodia has gained increasing interest among English lecturers and students in the Cambodian academic community.
Gradient Phonetic Implementation of Regressive Voicing Assimilation in Catalan Heterosyllabic Two- and Three-Consonant Clusters
Authors: Recasens Daniel 
Published: November 2014

Abstract
Electroglottographic data for word-final obstruents in C#C and CC#C sequences with a word-initial voiced consonant indicate that regressive voicing adaptation is a categorical and thus assimilatory process for most Catalan speakers. Word-final obstruents are planned as voiced since they exhibit full voicing or else an initial voicing period which is longer than the voicing lag associated with the vowel preceding the cluster. Segmental duration may also be used by speakers for realizing word-final obstruents as voiced in C#C but not in CC#C clusters. The phonetic implementation of voicing assimilation proceeds gradually: voicing for word-final obstruents differs considerably among speakers and is less for fricatives than for stops and whenever the word-initial consonant is an obstruent or an approximant than when it is a nasal, a lateral or an alveolar trill. The study also reveals that those C1 realizations which are less prone to acquire voicing show more token-totoken variability in voicing and segmental duration and therefore appear to be less tightly controlled by speakers. In conjunction with data from other studies, these Catalan data suggest that speakers and languages with prevoiced stops may differ with respect to the more or less gradient phonetic implementation of the regressive voicing assimilation process in heterosyllabic consonant clusters. © 2014 S. Karger AG, Basel