bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional interrogation of a depression-related serotonergic SNP, rs6295, using a humanized mouse model
Authors: Cunningham Ashley M. , Santos Tabia L. , Gutzeit Vanessa A. , Hamilton Heather , Hen René , Donaldson Zoe R. 
Published: November 2018

AbstractThe serotonin 1A receptor (5-HT1A) system has been extensively implicated in modulating mood and behavior. Notably, 5-HT1A levels in humans display remarkable variation and differences in receptor levels have been linked with a variety of psychiatric disorders. Further, manipulation of receptor levels in mice suggests that changes in receptor levels that model existing human variation are sufficient to drive behavioral alterations. As a result, genetic mechanisms that modulate human 5-HT1A levels may be important for explaining individual differences in mood and behavior, representing a potential source of psychiatric disease risk. One common genetic variant implicated in differential 5-HT1A levels is the G/C single nucleotide polymorphism (SNP), rs6295, located upstream of the human 5-HT1A gene. This SNP differentially binds the transcription factor, NUDR/Deaf1, leading to cell-type specific effects on transcription in vitro. To investigate the direct effects of this SNP in the heterogeneous cellular context of the brain, we generated humanized transgenic mice using a design that maximized the local transcriptional landscape of the human HTR1A gene while also controlling for effects of genomic insertion location. Expression of the human transgene in a 5-HT1A null mouse resulted in line-dependent expression of human 5-HT1A. The effect of rs6295 on protein levels and behavior similarly differed across lines, suggesting that the penetrance of rs6295 may depend upon background genetic factors. Together, this work confirms that relatively subtle differences in 5-HT1A levels can contribute to differences in behavior and highlights the challenges of modeling human non-coding genetic variation in mice.
Continuous chromatin state feature annotation of the human epigenome
Authors: Chen Bowen , Kenari Neda Shokraneh , Libbrecht Maxwell W 
Published: November 2018

AbstractSemi-automated genome annotation (SAGA) methods are widely used to understand genome activity and gene regulation. These methods take as input a set of sequencing-based assays of epigenomic activity (such as ChIP-seq measurements of histone modification and transcription factor binding), and output an annotation of the genome that assigns a chromatin state label to each genomic position. Existing SAGA methods have several limitations caused by the discrete annotation framework: such annotations cannot easily represent varying strengths of genomic elements, and they cannot easily represent combinatorial elements that simultaneously exhibit multiple types of activity. To remedy these limitations, we propose an annotation strategy that instead outputs a vector of chromatin state features at each position rather than a single discrete label. Continuous modeling is common in other fields, such as in topic modeling of text documents. We propose a method, epigenome-ssm, that uses a Kalman filter state space model to efficiently annotate the genome with chromatin state features. We show that chromatin state features from epigenome-ssm are more useful for several downstream applications than both continuous and discrete alternatives, including their ability to identify expressed genes and enhancers. Therefore, we expect that these continuous chromatin state features will be valuable reference annotations to be used in visualization and downstream analysis.
Transcriptome dynamics in developing leaves from C3and C4Flaveriaspecies reveal determinants of Kranz anatomy
Authors: Billakurthi Kumari , Wrobel Thomas J. , Bräutigam Andrea , Weber Andreas P.M. , Westhoff Peter , Gowik Udo 
Published: November 2018

AbstractC4species have evolved more than 60 times independently from C3ancestors. This multiple and parallel evolution of the complex C4trait indicates common underlying evolutionary mechanisms that might be identified by comparative analysis of closely related C3and C4species. Efficient C4function depends on a distinctive leaf anatomy that is characterized by enlarged, chloroplast rich bundle sheath cells and a narrow vein spacing. To elucidate molecular mechanisms generating this so called Kranz anatomy, we analyzed a developmental series of leaves from the C4plantFlaveria bidentisand the closely related C3speciesFlaveria robustausing leaf clearing and whole transcriptome sequencing. Applying non-negative matrix factorization on the data identified four different zones with distinct transcriptome patterns in growing leaves of both species. Comparing these transcriptome patterns revealed an important role of auxin metabolism and especially auxin homeostasis for establishing the high vein density typical for C4leaves.
Complete genome of a Measles virus from Roraima state, Brazil
Authors: Ribeiro Meneses Cátia Alexandra , Nascimento Valdinete Alves do , de Souza Victor Costa , Maito Rodrigo Melo , Aragão Gomes Marconi , Brígida Cunha Claudeth Rocha Santa , Antony Ilma de Aguiar , Silva Maria Eliane Oliveira e , Campos Daniela Palha de Souza , de Lima Guerra Corado André , Pessoa Karina Pinheiro , Monteiro Dana Cristina da Silva , Okumoto Osnei , Coelho Cunha Marília , Caselli Pacheco Flávia , Naveca Felipe Gomes 
Published: November 2018

SUMMARYMeasles is a human infectious disease of global concern caused by the measles virus. In this study, we report the complete genome sequencing of one measles isolate, genotype D8, obtained in Boa Vista city, the capital of the Roraima State, Brazil, directly from the urine sample. Phylogenetics reconstruction grouped the genome described in this study with samples from Australia, Italy, United Kingdom, and the USA. To our knowledge, this is the first complete genome of a wild-type measles virus from Latin America. Therefore, the present data strengthens the current knowledge about the molecular epidemiology of measles worldwide.SponsorshipsCNPq / CAPES / MS-DECIT / Fiocruz
Lifecycle-oriented design of ceramic tiles in sustainable supply chains (SSCs)
Authors: Settembre Blundo Davide , García Muiña Fernando Enrique , Pini Martina , Volpi Lucrezia , Siligardi Cristina , Ferrari Anna Maria 
Published: November 2018

Purpose
The purpose of this paper is to analyse the production cycle of glazed porcelain stoneware, from the extraction of raw materials to the packaging of the finished product, with the aim of verifying the effects of integrating an environmental impact assessment into the decision-making process for managing the life cycle, to make it economically and ecologically sustainable, in a holistic approach along the supply-chain.

Design/methodology/approach
The research is performed using the life cycle assessment and life cycle costing methodologies, to identify environmental impacts and costs, that occur during extraction of raw materials, transportation, ceramic tiles production, material handling, distribution and end-of-life stages within a cradle to grave perspective.

Findings
Through the use of a comprehensive analysis of the environmental impact assessment and related externalities, three possible strategic options to improve the environmental performance and costs of ceramic tile production were formulated, leveraging sustainability as a competitive advantage.

Research limitations/implications
This exploratory research opens future lines of investigation, the first of which is to confirm the technological feasibility and market responsiveness to the three strategic solutions hypothesised thanks to the use of an innovative eco-design technique.

Originality/value
The research has allowed testing and validating the tools of environmental impact assessment (life cycle assessment) and economic impact assessment (life cycle costing as structured methodologies in a life cycle management framework, to help companies implement competitive strategies based on sustainability.
Developing a European Standard for International Data Transfers after Snowden: Opinion 1/15 on the EU‐Canada PNR Agreement
Authors: Zalnieriute Monika 
Published: November 2018

AbstractIn Opinion 1/15 the Court of Justice of the European Union (CJEU) held that the proposed EU‐Canada Passenger Name Record (PNR) agreement must be revised because parts of it are incompatible with the EU fundamental rights framework. This note argues that the significance of Opinion 1/15 can only be understood in the broader historical context of increasing international securitisation between the 9/11 attacks in 2001 and the Snowden revelations in 2013. Opinion 1/15 emerges as a powerful addition to the existing data privacy trilogy established by the CJEU in the post‐Snowden era in an attempt to re‐balance the terms of international cooperation in data‐sharing between the EU and other countries. These terms were largely modelled around national security interests that have gained significant prominence in the aftermath of 9/11. While pro‐securitisation policies have been successful in gaining support among private and public actors, it is doubtful whether the CJEU pushback – without political support from EU Commission and Member States ‐ will achieve similar success.
Homicidal Paraquat Poisoning
Authors: Chen Fan , Ye Yi , Jin Bo , Yi Bo , Wei Qingtao , Liao Linchuan 
Published: November 2018

AbstractParaquat poisoning usually results from suicide, occupational, or accidental exposure. Herein, we report a rare fatal case of homicidal paraquat poisoning. A 58‐year‐old man was poisoned by taking paraquat‐mixed medicine and wearing paraquat‐soaked underwear. In the absence of a history of paraquat exposure, the patient was misdiagnosed with pulmonary infection and scrotal dermatitis and died of respiratory failure 24 days after the initial exposure to paraquat. Ultra‐performance liquid chromatography‐tandem mass spectrometry (UPLC‐MS/MS) was applied to detect and quantify paraquat in postmortem specimens. The concentration of paraquat in postmortem specimens from high to low is lung (0.49 μg/g), brain (0.32 μg/g), kidney (0.24 μg/g), liver (0.20 μg/g), cardiac blood (0.11 μg/mL), and stomach wall (<LOQ). Identification of homicidal paraquat poisoning is not easy for a clinician or a forensic pathologist, it is important to consider the possibility of paraquat poisoning when patients suffer from rapidly aggravating pneumonia of unknown origin.
HCN4 Gene Variations in Sudden Unexplained Nocturnal Death Syndrome in the Southern Han Chinese Population,
Authors: Wu Qiuping , Zhao Qianhao , Yin Kun , Hu Bing‐jie , Cheng Jianding 
Published: November 2018

AbstractSudden unexplained nocturnal death syndrome (SUNDS) is widely considered to be related to hereditary fatal arrhythmias. Hyperpolarization‐activated cyclic nucleotide‐gated channel 4 (HCN4) channels are widely distributed in sinus myocytes and play a profound role in generating pacemaker electro‐activity in cardiomyocytes. In the present study, the potential correlation between HCN4 gene variations and the occurrence of SUNDS was investigated. Genomic DNA was extracted from blood samples of both 119 unrelated SUNDS patients and 184 healthy individuals and screened for candidate HCN4 gene variants. One missense heterozygous variant c.1578C>T (Ala195Val) and four synonymous heterozygous variants c.1552C>T, c.2833C>T, c.3823C>T, and c.4189C>A were discovered in the SUNDS cases. The missense variant c.1578C>T (Ala195Val) was absent in 163 recruited controls and 105 persons of the Southern Han Chinese population, had in‐silico prediction indications as damaging, and was reported prevalent in sudden infant death, and is thus likely to be involved in SUNDS.
The CERN Community; A Mechanism for Effective Global Collaboration?
Authors: Robinson Mark 
Published: November 2018

AbstractGridlock is a term to describe the breakdown in cooperation of countries in international institutions to address policy problems that span borders; it refers both to deadlock in existing organisations and the difficulty of countries to come to new agreements as issues arise. Global science mega‐projects and their communities have seemingly been remarkably effective in evolving complex processes and mechanisms to enable collaboration. Previous research into CERN has focused on recounting the stories of CERN's scientific feats and technical innovations. This research has investigated the reasons behind these triumphs from a social sciences’ perspective to see why it is an exemplar of organisational success. The CERN communities’ governance and leadership regimes are examined. Extensive field work has added insights into two themes that emerge from the literature: the primacy of the state and the employment of combined routes through and beyond gridlock. Through exercising consensual governance with its Member States to manage multi‐polarity and using a light leadership approach with collaborative partners and international staff, CERN consistently achieves outstanding results. This research contributes to the global gridlock debate by being part of the examination of pathways and mechanisms in successful international collaborations.
PI3K activation within ventromedial prefrontal cortex regulates the expression of drug‐seeking in two rodent species
Authors: Szumlinski Karen K. , Ary Alexis W. , Shin Christina B. , Wroten Melissa G. , Courson Justin , Miller Bailey W. , Ruppert‐Majer Micaela , Hiller John W. , Shahin John R. , Ben‐Shahar Osnat , Kippin Tod E. 
Published: November 2018

AbstractPhosphatidylinositide 3‐kinases (PI3Ks) are intracellular signal transducer enzymes that recruit protein kinase B (aka Akt) to the cell membrane, the subsequent activation of which regulates many cellular functions. PI3K/Akt activity is up‐regulated within mesocorticolimbic structures in animal models of alcoholism, but less is known regarding PI3K/Akt activity in animal models of cocaine addiction. Given that prefrontal cortex (PFC) is grossly dysregulated in addiction, we studied how cocaine affects protein indices of PFC PI3K/Akt activity in rat and mouse models and examined the relevance of PI3K activity for cocaine‐related learning. Immunoblotting of mouse medial PFC at 3 weeks withdrawal from a cocaine‐sensitization regimen (seven injections of 30 mg/kg, intraperitoneal [IP]) revealed increased kinase activity, as did immunoblotting of tissue from the ventral PFC of rats with a history of long‐access intravenous cocaine self‐administration (0.25 mg/0.1 mL infusion; 10 days of 6 h/d cocaine access). Interestingly, increased Akt phosphorylation was observed in rat ventromedial PFC at both 3‐ and 30‐day withdrawal only in animals re‐exposed to cocaine‐associated cues. A conditioned place‐preference paradigm in mice and a cue‐elicited drug‐seeking test in rats were conducted to determine the functional relevance for elevated PI3K activity for addiction‐related behavior. In both cases, an intra‐PFC infusion of the PI3K inhibitor wortmannin (50μM) reduced drug‐seeking behavior. Taken together, this cross‐species, interdisciplinary, study provides convincing evidence that cocaine history produces an enduring increase in PI3K/Akt‐dependent signaling within the more ventral aspect of the PFC that is relevant to behavioral reactivity to drug‐associated cues/contexts. As such, PI3K inhibitors may well serve as an effective strategy for reducing drug cue reactivity and craving in cocaine addiction.
A comparison of embalming fluids on the structures and properties of tissue in human cadavers
Authors: Balta Joy Y. , Twomey Maria , Moloney Fiachra , Duggan Orla , Murphy Kevin P. , O’Connor Owen J. , Cronin Michael , Cryan John F. , Maher Michael M. , O’Mahony Siobhain M. 
Published: November 2018

AbstractCadaveric material has long been used to teach anatomy and more recently to train students in clinical skills. The aim of this study was to develop a systematic approach to compare the impact of four embalming solutions on the tissues of human cadavers. To this end, a formalin‐based solution, Thiel, Genelyn and Imperial College London soft‐preservation (ICL‐SP) solution were compared. The effect of these chemicals on the properties of the tissue was assessed by measuring the range of motion (ROM) of joints and measuring the dimensions of different structures on computed tomography (CT) images before and after embalming. The mean changes in the ratio (angle to ROM) differed statistically between embalming methods (Welch Statistic 3,1.672 = 67.213, p = 0.026). Thiel embalmed cadavers showed an increase in range of motion while ICL‐SP cadavers remained relatively the same. Genelyn and formalin embalmed cadavers registered a notable decrease in range of motion. Furthermore, investigation into the impact of the embalming chemicals on the dimensions of internal organs and vessels revealed that Thiel embalming technique leads to a decrease in the dimension of the cardiovascular system alone while formalin‐based solutions maintain the shape of the organs and vessels investigated. Our findings suggest that the joints of cadavers’ embalmed using ICL‐SP technique may faithfully mimic that of unembalmed cadavers and that formalin is necessary to retain shape and size of the organs and vessels investigated in this study. Despite this, a study with larger numbers of cadavers is required to confirm these findings.
Expression of glial cells molecules in the optic nerve of adult dromedary camel (Camelus dromedarius): A histological and immunohistochemical analysis
Authors: Metwally Elsayed , Farouk Sameh M. , Hossain Md Shafayat , Raihan Obayed 
Published: November 2018

AbstractThe optic nerve (ON) is an important organ in the visual system of animals, which transfers electrical impulses towards the brain from the retina. High enrichment of glial cells in ON is known to support neuron and regulate retinal homoeostasis. However, research on immunohistochemical of glial cells proteins in the camel is scanty in available literature. Hence, the current work is an attempt to investigate the histomorphology of camel ON with regard to the expression patterns of glial fibrillary acidic protein (GFAP), myelin basic protein (MBP) and Iba1 for the three glial subtypes, namely astrocytes, oligodendrocytes and microglia, respectively. Optic nerves from fourteen dromedary camels were dissected and preserved in 10% formalin. Then, the paraffin‐embedding sections were subjected for histochemical and immunohistochemical analysis. Our results demonstrated that ON axons aggregate into fascicles that surrounded by light and densely stained glial cells. Then, we examined the myelin sheath using Heidenhain's and Mallory's phosphotungstic acid staining. Immunoassay results revealed that GFAP is enriched in the ON and distributed evenly, whereas MBP and Iba1 were present at scanty levels. Further analysis of mRNA level of GFAP, MBP and Iba1 in the ON confirmed an elevation of GFAP expression compared to MBP and Iba1. We further found partial co‐localization of different types of glial cells that reflect their coordinated function in the ON. Although our data provide the first evidence for differential expression pattern of glial proteins, further molecular studies still required to reveal the specific function of these molecules in the camel ON.
Ventricular global longitudinal strain is altered in children with sickle cell disease
Authors: Whipple Nicholas S. , Naik Ronak J. , Kang Guolian , Moen Joseph , Govindaswamy Sarala D. , Fowler James A. , Dowdy Jolanta , Penkert Rhiannon , Joshi Vijaya M. , Hankins Jane S. 
Published: November 2018

SummaryCardiac disease is the primary cause of death in sickle cell disease (SCD). Right and left ventricular global longitudinal strain (RVGLS, LVGLS) are early markers of systolic dysfunction but are not well investigated among children with SCD. One hundred and forty‐three patients with HbSS or HbSβ0‐thalassaemia (median age 11 years, range 5–19 years) and 71 controls matched for age and sex were compared. RVGLS and LVGLS were measured and compared with conventional measures of echocardiography and markers of haemolysis and inflammation. RVGLS was higher in children with SCD than in controls (−25·72% ± 3·45% vs. −24·54% ± 2·41%, P = 0·005); LVGLS was not different. RVGLS decreased with older age in children with SCD (ρ = 0·338, P < 0·001) but not among controls. Decreased RVGLS was associated with increased left atrial end diastolic volume (ρ = 0·181, P = 0·04); RVGLS increased with cardiac output (r = −0·279, P = 0·01). RVGLS and LVGLS were not associated with disease‐modifying therapies, degree of anaemia or haemolysis markers. Elevated RVGLS may indicate an early RV compensatory mechanism in response to upstream myocardial insults and elevated cardiac output. Global longitudinal strain may serve as an early marker of altered myocardial function in children with SCD.
Genetic predisposition to PEG‐asparaginase hypersensitivity in children treated according to NOPHO ALL2008
Authors: Højfeldt Sofie G. , Wolthers Benjamin O. , Tulstrup Morten , Abrahamsson Jonas , Gupta Ramneek , Harila‐Saari Arja , Heyman Mats , Henriksen Louise T. , Jónsson Òlafur G. , Lähteenmäki Päivi M. , Lund Bendik , Pruunsild Kaie , Vaitkeviciene Goda , Schmiegelow Kjeld , Albertsen Birgitte K. ,   the Nordic Society of Paediatric Haematology Oncology (NOPHO) group
Published: November 2018

SummaryAsparaginase is essential in childhood acute lymphoblastic leukaemia (ALL) treatment, however hypersensitivity reactions to pegylated asparaginase (PEG‐asparaginase) hampers anti‐neoplastic efficacy. Patients with PEG‐asparaginase hypersensitivity have been shown to possess zero asparaginase enzyme activity. Using this measurement to define the phenotype, we investigated genetic predisposition to PEG‐asparaginase hypersensitivity in a genome‐wide association study (GWAS). From July 2008 to March 2016, 1494 children were treated on the Nordic Society of Paediatric Haematology and Oncology ALL2008 protocol. Cases were defined by clinical hypersensitivity and no enzyme activity, controls had enzyme activity ≥ 100 iu/l and no hypersensitivity symptoms. PEG‐asparaginase hypersensitivity was reported in 13·8% (206/1494) of patients. Fifty‐nine cases and 772 controls fulfilled GWAS inclusion criteria. The CNOT3 variant rs73062673 on 19q13.42, was associated with PEG‐asparaginase allergy (P = 4·68 × 10−8). We further identified two signals on chromosome 6 in relation to HLA‐DQA1 (P = 9·37 × 10−6) and TAP2 (P = 1·59 × 10−5). This study associated variants in CNOT3 and in the human leucocyte antigen (HLA) region with PEG‐asparaginase hypersensitivity, suggesting that not only genetic variations in the HLA region, but also regulation of these genes are of importance in the biology of this toxicity. Furthermore, our study emphasizes the importance of using asparaginase enzyme activity measurements to identify PEG‐asparaginase hypersensitivity.