bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of a multimodal set‐up for the study of zirconium alloys claddings' behaviour under simulated LOCA conditions
Authors: Campello D. , Tardif N. , Desquines J. , Baietto M.‐C. , Coret M. , Maynadier A. , Chaudet P. 
Published: June 2018

AbstractIn a previous paper, Campello et al. presented a combined experimental/numerical approach to identify the creep behaviour of as‐fabricated Zircaloy‐4 claddings under simulated LOCA conditions. The current paper deals with the uncertainties and errors estimation of the two key methods used to measure the thermal and kinematic full fields during the creep tests: near infrared thermography (NIRT) and two‐dimensional digital image correlation (2D‐DIC).The NIRT uncertainties are evaluated as 0.7% of the actual temperature. They are mainly due to the thermocouple measurements used to calibrate the radiometric model of the NIRT.A combined 2D‐DIC/edge detection approach is proposed to quantify the error related to 2D‐DIC when measuring the ballooning of the tubular specimen. The 2D‐DIC error is evaluated as 0.1% of the actual equivalent strain even for ballooning inducing a radius increase of 20%.
In vivo lipid ‘tag and track’ approach shows acyl editing of plastid lipids and chloroplast import of phosphatidylglycerol precursors in Arabidopsis thaliana
Authors: Hurlock Anna K. , Wang Kun , Takeuchi Tomomi , Horn Patrick J. , Benning Christoph 
Published: June 2018

SummaryIn plant lipid metabolism, the synthesis of many intermediates or end products often appears overdetermined with multiple synthesis pathways acting in parallel. Lipid metabolism is also dynamic with interorganelle transport, turnover, and remodeling of lipids. To explore this complexity in vivo, we developed an in vivo lipid ‘tag and track’ method. Essentially, we probed the lipid metabolism in Arabidopsis thaliana by expressing a coding sequence for a fatty acid desaturase from Physcomitrella patens (Δ6D). This enzyme places a double bond after the 6th carbon from the carboxyl end of an acyl group attached to phosphatidylcholine at its sn‐2 glyceryl position providing a subtle, but easily trackable modification of the glycerolipid. Phosphatidylcholine is a central intermediate in plant lipid metabolism as it is modified and converted to precursors for other lipids throughout the plant cell. Taking advantage of the exclusive location of Δ6D in the endoplasmic reticulum (ER) and its known substrate specificity for one of the two acyl groups on phosphatidylcholine, we were able to ‘tag and track’ the distribution of lipids within multiple compartments and their remodeling in transgenic lines of different genetic backgrounds. Key findings were the presence of ER‐derived precursors in plastid phosphatidylglycerol and prevalent acyl editing of thylakoid lipids derived from multiple pathways. We expect that this ‘tag and track’ method will serve as a tool to address several unresolved aspects of plant lipid metabolism, such as the nature and interaction of different subcellular glycerolipid pools during plant development or in response to adverse conditions.
Cannabinoid receptor types 1 and 2 and peroxisome proliferator‐activated receptor‐α: distribution in the skin of clinically healthy cats and cats with hypersensitivity dermatitis
Authors: Miragliotta Vincenzo , Ricci Pier Luca , Albanese Francesco , Pirone Andrea , Tognotti Danika , Abramo Francesca 
Published: June 2018

BackgroundCannabinoid receptors and peroxisome proliferator‐activated receptor‐alpha (PPAR‐α) are gaining recognition as potential therapeutic targets for the treatment of skin disorders.Hypothesis/ObjectivesThe aim of this study was to investigate the distribution of cannabinoid type 1 and 2 receptors (CBR1 and CBR2) and PPAR‐α in feline skin and verify whether changes occur in the course of hypersensitivity dermatitis.AnimalsTwelve privately owned cats. Skin samples were obtained from five healthy cats with no skin lesions and seven cats clinically diagnosed with hypersensitivity dermatitis.Methods and materialsHaematoxylin and eosin stained skin sections were investigated for histopathological changes. Indirect immunofluorescence for CBR1, CBR2 and PPAR‐α was performed on paraffin‐embedded sections, and antibody specificity tested by Western blot analysis.ResultsSkin samples from cats with hypersensitivity dermatitis were all histopathologically diagnosed with eosinophilic dermatitis. CB receptors and PPAR‐α were distributed throughout the skin in both healthy and allergic cats. In normal feline skin, these receptors were mainly distributed in the epithelial compartment. Receptor expression increased in hypersensitivity compared to healthy skin, with the main distribution changes being suprabasal for CBR1, dermal for CBR2 and marked expression of PPAR‐α in hyperplastic epidermis and perivascular infiltrate.Conclusions and clinical importanceIncreased expression of cannabinoid receptors in the skin of cats with hypersensitivity dermatitis suggests an endogenous protective strategy and may support the use of natural cannabinoid receptor or PPAR‐α agonists to treat feline hypersensitivity dermatitis.
A structurally derived model of subunit‐dependent NMDA receptor function
Authors: Gibb Alasdair J. , Ogden Kevin K. , McDaniel Miranda J. , Vance Katie M. , Kell Steven A. , Butch Chris , Burger Pieter , Liotta Dennis C. , Traynelis Stephen F. 
Published: June 2018

Key points
The kinetics of NMDA receptor (NMDAR) signalling are a critical aspect of the physiology of excitatory synaptic transmission in the brain.
Here we develop a mechanistic description of NMDAR function based on the receptor tetrameric structure and the principle that each agonist‐bound subunit must undergo some rate‐limiting conformational change after agonist binding, prior to channel opening.
By fitting this mechanism to single channel data using a new MATLAB‐based software implementation of maximum likelihood fitting with correction for limited time resolution, rate constants were derived for this mechanism that reflect distinct structural changes and predict the properties of macroscopic and synaptic NMDAR currents.
The principles applied here to develop a mechanistic description of the heterotetrameric NMDAR, and the software used in this analysis, can be equally applied to other heterotetrameric glutamate receptors, providing a unifying mechanistic framework to understanding the physiology of glutamate receptor signalling in the brain.
AbstractNMDA receptors (NMDARs) are tetrameric complexes comprising two glycine‐binding GluN1 and two glutamate‐binding GluN2 subunits. Four GluN2 subunits encoded by different genes can produce up to 10 different di‐ and triheteromeric receptors. In addition, some neurological patients contain a de novo mutation or inherited rare variant in only one subunit. There is currently no mechanistic framework to describe tetrameric receptor function that can be extended to receptors with two different GluN1 or GluN2 subunits. Here we use the structural features of glutamate receptors to develop a mechanism describing both single channel and macroscopic NMDAR currents. We propose that each agonist‐bound subunit undergoes some rate‐limiting conformational change after agonist binding, prior to channel opening. We hypothesize that this conformational change occurs within a triad of interactions between a short helix preceding the M1 transmembrane helix, the highly conserved M3 motif encoded by the residues SYTANLAAF, and the linker preceding the M4 transmembrane helix of the adjacent subunit. Molecular dynamics simulations suggest that pre‐M1 helix motion is uncorrelated between subunits, which we interpret to suggest independent subunit‐specific conformational changes may influence these pre‐gating steps. According to this interpretation, these conformational changes are the main determinants of the key kinetic properties of NMDA receptor activation following agonist binding, and so these steps sculpt their physiological role. We show that this structurally derived tetrameric model describes both single channel and macroscopic data, giving a new approach to interpreting functional properties of synaptic NMDARs that provides a logical framework to understanding receptors with non‐identical subunits.
6S RNA, a Global Regulator of Transcription
Authors: Wassarman Karen M. 
Published: June 2018

ABSTRACT

6S RNA is a small RNA regulator of RNA polymerase (RNAP) that is present broadly throughout the bacterial kingdom. Initial functional studies in
Escherichia coli
revealed that 6S RNA forms a complex with RNAP resulting in regulation of transcription, and cells lacking 6S RNA have altered survival phenotypes. The last decade has focused on deepening the understanding of several aspects of 6S RNA activity, including (i) addressing questions of how broadly conserved 6S RNAs are in diverse organisms through continued identification and initial characterization of divergent 6S RNAs; (ii) the nature of the 6S RNA-RNAP interaction through examination of variant proteins and mutant RNAs, cross-linking approaches, and ultimately a cryo-electron microscopic structure; (iii) the physiological consequences of 6S RNA function through identification of the 6S RNA regulon and promoter features that determine 6S RNA sensitivity; and (iv) the mechanism and cellular impact of 6S RNA-directed synthesis of product RNAs (i.e., pRNA synthesis). Much has been learned about this unusual RNA, its mechanism of action, and how it is regulated; yet much still remains to be investigated, especially regarding potential differences in behavior of 6S RNAs in diverse bacteria.
Divergent Small Tim Homologues Are Associated with TbTim17 and Critical for the Biogenesis of TbTim17 Protein Complexes in
Trypanosoma brucei
Authors: Smith Joseph T. , Singha Ujjal K. , Misra Smita , Chaudhuri Minu 
Published: June 2018

Trypanosoma brucei
is the causative agent of African sleeping sickness. The parasite’s mitochondrion represents a useful source for potential chemotherapeutic targets. Similarly to yeast and humans, mitochondrial functions depend on the import of proteins that are encoded in the nucleus and made in the cytosol. Even though the machinery involved in this mitochondrial protein import process is becoming clearer in
T. brucei
, a comprehensive picture of protein complex composition and function is still lacking. In this study, we characterized three
T. brucei
small Tim proteins, TbTim9, TbTim10, and TbTim8/13. Although the parasite does not have the classical TIM22 complex that imports mitochondrial inner membrane proteins containing internal targeting signals in yeast or humans, we found that these small TbTims associate with TbTim17, the major subunit of the TbTIM complex in
T. brucei
, and play an essential role in the stability of the TbTim17 complexes. Therefore, these divergent proteins are critical for mitochondrial protein biogenesis in
T. brucei
.
Persistence of Resident and Transplanted Genotypes of the Undomesticated Yeast Saccharomyces paradoxus in Forest Soil
Authors: Anderson James B. , Kasimer Dahlia , Xia Wenjing , Schröder Nicolas C. H. , Cichowicz Patrick , Lioniello Silvio , Chakrabarti Rudrakshi , Mohan Eashwar , Kohn Linda M. 
Published: June 2018

Saccharomyces
yeasts are intensively studied in biological research and in their domesticated roles in brewing and baking, and yet, remarkably little is known about their mode of life in forest soils. We report here that resident genotypes of the yeast
S. paradoxus
are persistent on a time scale of years in their microhabitats in forest soils. We also show that resident genotypes can be replaced by transplanted yeast genotypes. The high inoculum levels in experimental transplantations rapidly decreased over time, but the transplanted genotypes persisted at low abundance. We conclude that, in forest soils,
Saccharomyces
yeasts exist at very low abundance and that dispersal events are rare.
Self-reported child abuse in the home: a cross-sectional survey of prevalence, perpetrator characteristics and correlates among public secondary school students in Kathmandu, Nepal
Authors: Neupane Dipika , Bhandari Parash Mani , Thapa Kiran , Bhochhibhoya Shristi , Rijal Shristi , Pathak Ramjee Prasad 
Published: June 2018

ObjectivesTo explore the prevalence, perpetrator characteristics and the correlates of child abuse in Kathmandu, Nepal.MethodsFor this cross-sectional study, we translated the internationally validated questionnaire developed by the International Society for Prevention of Child Abuse and Neglect, Child Abuse Screening Tool-Child Home into Nepali. We added questions on descriptive information about students and their family to the questionnaire. We recruited students from 20 schools selected randomly—2 from each of the 10 electoral constituencies of Kathmandu district. In each school, we administered the questionnaires to the students in a classroom selected randomly. To assess the correlates, we ran multilevel multivariable logistic regression models, stratified by schools.ResultsAmong the 962 students, 88.88% had experience of at least one form of abuse throughout their lifetime. Psychological abuse was the most prevalent form of abuse (previous year: 75.19%; lifetime: 76.15%) followed by physical abuse, exposure to violence, neglect and sexual abuse. Adults were the most common perpetrators of child abuse (37.55%). The correlates identified in this study mostly aligned with the global literature on correlates of abuse. Female students were more likely to report neglect (previous year: adjusted OR (AOR) 1.50, 95% CI 1.10 to 2.04; lifetime: AOR 1.49, 95% CI 1.10 to 2.02), but no gender difference was observed with other forms of abuse. Students living with a single parent had a greater likelihood of exposure to violence (previous year: AOR 2.55, 95% CI 1.31 to 4.94; lifetime: AOR 2.77, 95% CI 1.39 to 5.53), neglect (previous year: AOR 2.01, 95% CI 1.10 to 3.69; lifetime: AOR 2.08, 95% CI 1.14 to 3.81) and sexual abuse (previous year: AOR 3.03, 95% CI 1.45 to 6.37; lifetime: AOR 2.49, 95% CI 1.21 to 5.14).ConclusionsOver 88% of students reported experiencing child abuse in the home in one or more forms throughout their lifetime. Delineating the reasons for the high burden and its implications are important topics for future research.
Estimating the economic costs of ethnic health inequities: protocol for a prevalence-based cost-of-illness study in New Zealand (2003–2014)
Authors: Reid Papaarangi , Paine Sarah-Jane , Te Ao Braden , Willing Esther , Wyeth Emma , Vaithianathan Rhema 
Published: June 2018

IntroductionThere is significant international interest in the economic impacts of persistent inequities in morbidity and mortality. However, very few studies have quantified the costs associated with unfair and preventable ethnic/racial inequities in health. The proposed study will investigate inequities in health between the indigenous Māori and non-Māori adult population in New Zealand (15 years and older) and estimate the economic costs associated with these differences.Methods and analysisThe study will use national collections data that is held by government agencies in New Zealand including hospitalisations, mortality, outpatient consultations, laboratory and pharmaceutical claims, and accident compensation claims. Epidemiological methods will be used to calculate prevalences for Māori and non-Māori, by age-group, gender and socioeconomic deprivation (New Zealand Deprivation Index) where possible. Rates of ‘potentially avoidable’ hospitalisations and mortality as well as ‘excess or under’ utilisation of healthcare will be calculated as the difference between the actual rate and that expected if Māori were to have the same rates as non-Māori. A prevalence-based cost-of-illness approach will be used to estimate health inequities and the costs associated with treatment, as well as other financial and non-financial costs (such as years of life lost) over the person’s lifetime.Ethics and disseminationThis analysis has been approved by the University of Auckland Human Participants Research Committee (Ref: 018621). Dissemination of findings will occur via published peer-reviewed articles, presentations to academic, policy and community-based stakeholder groups and via social media.
Outcomes of beta blocker use in cocaine-associated chest pain: a meta-analysis
Authors: Pham Don , Addison Daniel , Kayani Waleed , Misra Arunima , Jneid Hani , Resar Jon , Lakkis Nassir , Alam Mahboob 
Published: June 2018

ObjectivesBeta blockers (β-blockers) remain a standard therapy in the early treatment of acute coronary syndromes. However, β-blocker therapy in patients with cocaine-associated chest pain (CACP) continues to be an area of debate due to the potential risk of unopposed α-adrenergic stimulation and coronary vasospasm. Therefore, we performed a systematic review and meta-analysis of available studies to compare outcomes of β-blocker versus no β-blocker use among patients with CACP.MethodsWe searched the MEDLINE and EMBASE databases through September 2016 using the keywords ‘beta blocker’, ‘cocaine’ and commonly used β-blockers (‘atenolol’, ‘bisoprolol’, ‘carvedilol’, ‘esmolol’, ‘metoprolol’ and ‘propranolol’) to identify studies evaluating β-blocker use among patients with CACP. We specifically focused on studies comparing outcomes between β-blocker versus no β-blocker usage in patients with CACP. Studies without a comparison between β-blocker and no β-blocker use were excluded. Outcomes of interest included non-fatal myocardial infarction (MI) and all-cause mortality. Quantitative data synthesis was performed using a random-effects model and heterogeneity was assessed using Q and I2statistics.ResultsA total of five studies evaluating 1794 subjects were included. Overall, there was no significant difference on MI in patients with CACP on β-blocker versus no β-blocker (OR 1.36, 95% CI 0.68 to 2.75; p=0.39). Similarly, there was no significant difference in all-cause mortality in patients on β-blocker versus no β-blocker (OR 0.68, 95% CI 0.26 to 1.79; p=0.43).ConclusionsIn patients presenting with acute chest pain and underlying cocaine, β-blocker use does not appear to be associated with an increased risk of MI or all-cause mortality.
Epithelial–Mesenchymal Transition in Human Prostate Cancer Demonstrates Enhanced Immune Evasion Marked by IDO1 Expression
Authors: Kolijn Kimberley , Verhoef Esther I. , Smid Marcel , Böttcher René , Jenster Guido W. , Debets Reno , van Leenders Geert J.L.H. 
Published: June 2018

Abstract
Cancer invasion and metastasis are driven by epithelial–mesenchymal transition (EMT), yet the exact mechanisms that account for EMT in clinical prostate cancer are not fully understood. Expression of N-cadherin is considered a hallmark of EMT in clinical prostate cancer. In this study, we determined the molecular mechanisms associated with N-cadherin expression in patients with prostate cancer. We performed laser capture microdissection of matched N-cadherin–positive and -negative prostate cancer areas from patient samples (n = 8), followed by RNA sequencing. N-cadherin expression was significantly associated with an immune-regulatory signature including profound upregulation of indoleamine 2,3-dioxygenase (IDO1; log2-fold change = 5.1; P = 2.98E-04). Fluorescent immunostainings of patient samples confirmed expression of IDO1 protein and also its metabolite kynurenine in primarily N-cadherin–positive areas. N-cadherin–positive areas also exhibited a local decrease of intraepithelial cytotoxic (CD8+) T cells and an increase of immunosuppressive regulatory T cells (CD4+/FOXP3+). In conclusion, EMT in clinical prostate cancer is accompanied by upregulated expression of IDO1 and an increased number of regulatory T cells. These data indicate that EMT, which is an important step in tumor progression, can be protected from effective immune control in patients with prostate cancer.
Significance: These findings demonstrate EMT is linked to an immunosuppressive environment in clinical prostate cancer, suggesting that patients with prostate cancer can potentially benefit from combinatorial drug therapy. Cancer Res; 78(16); 4671–9. ©2018 AACR.
Inactivation of Citron Kinase Inhibits Medulloblastoma Progression by Inducing Apoptosis and Cell Senescence
Authors: Pallavicini Gianmarco , Sgrò Francesco , Garello Francesca , Falcone Mattia , Bitonto Valeria , Berto Gaia E. , Bianchi Federico T. , Gai Marta , Chiotto Alessandra M.A. , Filippi Miriam , Cutrin Juan C. , Ala Ugo , Terreno Enzo , Turco Emilia , Cunto Ferdinando Di 
Published: June 2018

AbstractMedulloblastoma is the most common malignant brain tumor in children. Current treatment for medulloblastoma consists of surgery followed by irradiation of the whole neuraxis and high-dose multiagent chemotherapy, a partially effective strategy associated with highly invalidating side effects. Therefore, identification and validation of novel target molecules capable of contrasting medulloblastoma growth without disturbing brain development is needed. Citron kinase protein (CITK), encoded by primary microcephaly gene MCPH17, is required for normal proliferation and survival of neural progenitors. Constitutive loss of CITK leads to cytokinesis failure, chromosome instability, and apoptosis in the developing brain, but has limited effects on other tissues. On this basis, we hypothesized that CITK could be an effective target for medulloblastoma treatment. In medulloblastoma cell lines DAOY and ONS-76, CITK knockdown increased both cytokinesis failure and DNA damage, impairing proliferation and inducing cell senescence and apoptosis via TP53 or TP73. Similar effects were obtained in the NeuroD-SmoA1 transgenic mouse model, in which CITK deletion increased apoptotic cells and senescence markers such as P21CIP1, P27KIP1, and P16INK4A. Most importantly, CITK deletion decreased tumor growth and increased overall survival in these mice, with no apparent side effects. These results suggest that CITK can be a useful molecular target for medulloblastoma treatment.Significance: In vitro and in vivo proof of concept identifies citron kinase protein as a suitable target for medulloblastoma treatment.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/16/4599/F1.large.jpg. Cancer Res; 78(16); 4599–612. ©2018 AACR.