bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activities and specificities of CRISPR/Cas9 and Cas12a nucleases for targeted mutagenesis in maize
Authors: Lee Keunsub , Zhang Yingxiao , Kleinstiver Benjamin P. , Guo Jimmy A. , Aryee Martin J. , Miller Jonah , Malzahn Aimee , Zarecor Scott , Lawrence‐Dill Carolyn J. , Joung J. Keith , Qi Yiping , Wang Kan 
Published: July 2018

SummaryCRISPR/Cas9 and Cas12a (Cpf1) nucleases are two of the most powerful genome editing tools in plants. In this work, we compared their activities by targeting maize glossy2 gene coding region that has overlapping sequences recognized by both nucleases. We introduced constructs carrying SpCas9‐guide RNA (gRNA) and LbCas12a‐CRISPR RNA (crRNA) into maize inbred B104 embryos using Agrobacterium‐mediated transformation. On‐target mutation analysis showed that 90%–100% of the Cas9‐edited T0 plants carried indel mutations and 63%–77% of them were homozygous or biallelic mutants. In contrast, 0%–60% of Cas12a‐edited T0 plants had on‐target mutations. We then conducted CIRCLE‐seq analysis to identify genome‐wide potential off‐target sites for Cas9. A total of 18 and 67 potential off‐targets were identified for the two gRNAs, respectively, with an average of five mismatches compared to the target sites. Sequencing analysis of a selected subset of the off‐target sites revealed no detectable level of mutations in the T1 plants, which constitutively express Cas9 nuclease and gRNAs. In conclusion, our results suggest that the CRISPR/Cas9 system used in this study is highly efficient and specific for genome editing in maize, while CRISPR/Cas12a needs further optimization for improved editing efficiency.
Loneliness, HPA stress reactivity and social threat sensitivity: Analyzing naturalistic social challenges
Authors: Nowland Rebecca , Robinson Sarita J. , Bradley Belinda F. , Summers Vikki , Qualter Pamela 
Published: July 2018

Loneliness has been linked to poor health through an increased activation of threat surveillance mechanisms, such as the hypothalamic‐pituitary‐adrenal axis (HPA). The socio‐cognitive model (Cacioppo & Hawley) proposes that lonely people have an increased social threat sensitivity which activates the HPA axis. The current study examined the impact of loneliness on HPA stress reactivity and social threat sensitivity in response to naturally occurring social challenges. Participants (N = 45) were prospective undergraduates attending a 3‐day university preparation programme over the summer, prior to commencing their university studies. Cortisol levels and perceived stress were measured before and after an ice breaker session on Day 1 and a lecture session on Day 3. Social threat sensitivity was also measured on the first and third day. When meeting unfamiliar peers in the ice breaker session, HPA stress reactivity was evident, but it was not markedly different in those who reported high levels of loneliness than those with low levels. The high loneliness group had higher levels of perceived stress and increased social threat sensitivity than the low loneliness group on both testing days. The findings show partial support for the socio‐cognitive model of loneliness because increased threat sensitivity was demonstrated in the high loneliness group. The findings indicate that lonely people do not respond in a physiologically different way to specific social challenges, but they typically report higher social threat sensitivity and higher perceived stress than their non‐lonely peers.
Reviewer Acknowledgements
Authors: Young James 
Published: July 2018

International Journal of Social Science Studies (IJSSS) would like to acknowledge the following reviewers for their assistance with peer review of manuscripts for this issue. Many authors, regardless of whether IJSSS publishes their work, appreciate the helpful feedback provided by the reviewers. Their comments and suggestions were of great help to the authors in improving the quality of their papers. Each of the reviewers listed below returned at least one review for this issue.Reviewers for Volume 6, Number 7 Abdul Azim Akhtar, Independent Academic & Researcher, Delhi, IndiaBegoña Montero-Fleta, Universitat Politécnica de València, SpainEnzo Loner, University of Trento, ItalyFroilan Mobo, Philippine Merchant Marine Academy, PhilippinesJehu Onyekwere Nnaji, University of Naples II, Italy and Globe Visions Network Italy, ItalyJianquan Cheng, Manchester Metropolitan University, UKJulia M. Mack, Gannon University, USAK.O. Aramide, The Polytechnic Ibadan, NigeriaMei-Ling Lin, National Open University, TaiwanMohammad Naji Shah Mohammadi, Kuala Lumpur, MalaysiaQingzhi Huan, Peking University, ChinaRachita Shrivastava Roy, Department of Higher Education,Chhatisgarh-India, IndiaShariq aziz butt, Superior University Lahore, PakistanXian-Liang Tian, Zhongnan University of Economics and Law, ChinaZlatan Begić, University of Tuzla, Bosnia and Herzegovina
Maternal obesity has sex‐dependent effects on insulin, glucose and lipid metabolism and the liver transcriptome in young adult rat offspring
Authors: Lomas‐Soria Consuelo , Reyes‐Castro Luis A. , Rodríguez‐González Guadalupe L. , Ibáñez Carlos A. , Bautista Claudia J. , Cox Laura A. , Nathanielsz Peter W. , Zambrano Elena 
Published: July 2018

Key points
Maternal high‐fat diet consumption predisposes to metabolic dysfunction in male and female offspring at young adulthood.
Maternal obesity programs non‐alcoholic fatty liver disease (NAFLD) in a sex‐dependent manner.
We demonstrate sex‐dependent liver transcriptome profiles in rat offspring of obese mothers.
In this study, we focused on pathways related to insulin, glucose and lipid signalling.
These results improve understanding of the mechanisms by which a maternal high‐fat diet affects the offspring.
AbstractMaternal obesity (MO) predisposes offspring (F1) to obesity, insulin resistance (IR) and non‐alcoholic fatty liver disease (NAFLD). MO's effects on the F1 liver transcriptome are poorly understood. We used RNA‐seq to determine the liver transcriptome of male and female F1 of MO and control‐fed mothers. We hypothesized that MO‐F1 are predisposed to sex‐dependent adult liver dysfunction. Female Wistar rat mothers ate a control (C) or obesogenic (MO) diet from the time they were weaned through breeding at postnatal day (PND) 120, delivery and lactation. After weaning, all male and female F1 ate a control diet. At PND 110, F1 serum, liver and fat were collected to analyse metabolites, histology and liver differentially expressed genes. Male and female MO‐F1 showed increased adiposity index, triglycerides, insulin and homeostatic model assessment vs. C‐F1 with similar body weight and glucose serum concentrations. MO‐F1 males presented greater physiological and histological NAFLD characteristics than MO‐F1 females. RNA‐seq revealed 1365 genes significantly changed in male MO‐F1 liver and only 70 genes in female MO‐F1 compared with controls. GO and KEGG analysis identified differentially expressed genes related to metabolic processes. Male MO‐F1 liver showed the following altered pathways: insulin signalling (22 genes), phospholipase D signalling (14 genes), NAFLD (13 genes) and glycolysis/gluconeogenesis (7 genes). In contrast, few genes were altered in these pathways in MO‐F1 females. In summary, MO programs sex‐dependent F1 changes in insulin, glucose and lipid signalling pathways, leading to liver dysfunction and insulin resistance.
α2δ‐1 couples to NMDA receptors in the hypothalamus to sustain sympathetic vasomotor activity in hypertension
Authors: Ma Huijie , Chen Shao‐Rui , Chen Hong , Zhou Jing‐Jing , Li De‐Pei , Pan Hui‐Lin 
Published: July 2018

Key points
α2δ‐1 is upregulated, promoting the interaction with NMDA receptors (NMDARs), in the hypothalamus in a rat model of hypertension.
The prevalence of α2δ‐1–bound NMDARs at synaptic sites in the hypothalamus is increased in hypertensive animals.
α2δ‐1 is essential for the increased presynaptic and postsynaptic NMDAR activity of hypothalamic neurons in hypertension.
α2δ‐1–bound NMDARs in the hypothalamus are critically involved in augmented sympathetic outflow in hypertensive animals.
AbstractIncreased glutamate NMDA receptor (NMDAR) activity in the paraventricular nucleus (PVN) of the hypothalamus leads to augmented sympathetic outflow in hypertension. However, the molecular mechanisms underlying this effect remain unclear. α2δ‐1, previously considered to be a voltage‐activated calcium channel subunit, is a newly discovered powerful regulator of NMDARs. In the present study, we determined the role of α2δ‐1 in regulating synaptic NMDAR activity of rostral ventrolateral medulla (RVLM)‐projecting PVN neurons in spontaneously hypertensive rats (SHRs). We show that the protein levels of α2δ‐1 and NMDARs in synaptosomes and the α2δ‐1–NMDAR complexes in the hypothalamus were substantially higher in SHRs than in normotensive control rats. The basal amplitude of evoked NMDAR currents and NMDAR‐mediated synaptic glutamate release in RVLM‐projecting PVN neurons were significantly increased in SHRs. Strikingly, inhibiting α2δ‐1 activity with gabapentin or disrupting the α2δ‐1–NMDAR association with an α2δ‐1 C‐terminus peptide completely normalized the amplitude of evoked NMDAR currents and NMDAR‐mediated synaptic glutamate release in RVLM‐projecting PVN neurons in SHRs. In addition, microinjection of the α2δ‐1 C‐terminus peptide into the PVN substantially reduced arterial blood pressure and renal sympathetic nerve discharges in SHRs. Our findings indicate that α2δ‐1–bound NMDARs in the PVN are required for the potentiated presynaptic and postsynaptic NMDAR activity of PVN presympathetic neurons and for the elevated sympathetic outflow in hypertension. α2δ‐1–bound NMDARs may be an opportune target for treating neurogenic hypertension.
Rapid assessment of avoidable blindness and diabetic retinopathy in people aged 50 years and older in the National Capital District of Papua New Guinea
Authors: Burnett Anthea , Lee Ling , D'Esposito Fabrizio , Wabulembo Geoffrey , Cama Anaseini , Guldan Georgia , Nelisse Marleen , Koim Samuel Peter , Keys Drew , Poffley Alison J , Limburg Hans , Garap Jambi 
Published: July 2018

Background/aimsTo conduct an assessment of avoidable blindness, diabetes mellitus and diabetic retinopathy (DR) in adults aged 50 years and older in the National Capital District (NCD) region of Papua New Guinea (PNG).MethodsA cross-sectional population-based survey was performed for which 25 clusters of 50 people aged ≥50 years were randomly selected from the NCD region. The standardised rapid assessment of avoidable blindness (RAAB) with diabetic retinopathy (+DR) methodology was used. Blindness was defined as presenting visual acuity <3/60 in the better eye. Participants were classified as having diabetes if they were known to have diabetes or if their random blood glucose level was ≥200 mg/dL. Dilated fundus examination and Scottish DR grading were performed.ResultsIn total, 1192 out of 1250 eligible participants (95.4%) were examined. Of these, 7.8% had known or newly diagnosed diabetes. Seventy-one per cent of participants with known diabetes had a blood glucose level ≥200 mg/dL, and 82.9% had never had an ophthalmological examination for DR. Prevalence of DR and/or maculopathy was 46.4%. The age-adjusted and sex-adjusted prevalence of diabetes was estimated at 8.1% (95% CI 5.7% to 10.4%) in the population aged 50 years or older in the NCD region of PNG.ConclusionsPrevalence of diabetes in adults aged 50 years and older was lower than reported elsewhere in the region, and lower than other RAAB+DR surveys. Despite this, the prevalence of DR is high compared with other RAAB+DR surveys and demonstrates the need for increased awareness and accessibility to eye services for people with diabetes.
Accuracy of trained rural ophthalmologists versus non-medical image graders in the diagnosis of diabetic retinopathy in rural China
Authors: McKenna Martha , Chen Tingting , McAneney Helen , Vázquez Membrillo Miguel Angel , Jin Ling , Xiao Wei , Peto Tunde , He Mingguang , Hogg Ruth , Congdon Nathan 
Published: July 2018

Background/aimsTo determine the diagnostic accuracy of trained rural ophthalmologists and non-medical image graders in the assessment of diabetic retinopathy (DR) in rural China.MethodsConsecutive patients with diabetes mellitus were examined from January 2014 to December 2015 at 10 county-level facilities in rural Southern China. Trained rural ophthalmologists performed a complete eye examination, recording diagnoses using the UK National Diabetic Eye Screening Programme (NDESP) classification system. Two field, mydriatic, 45° digital photographs were made by nurses using NDESP protocols and graded by trained graders with no medical background using the NDESP system. A fellowship-trained retina specialist graded all images in masked fashion and served as reference standard.ResultsAltogether, 375 participants (mean age 60±10 years, 48% men) were examined and 1277 images were graded. Grader sensitivity (0.82–0.94 (median 0.88)) and specificity (0.91–0.99 (median 0.98)), reached or exceeded NDESP standards (sensitivity 80%, specificity 95%) in all domains except specificity detecting any DR. Rural ophthalmologists’ sensitivity was 0.65–0.95 (median 0.66) and specificity 0.59–0.95 (median 0.91). There was strong agreement between graders and the reference standard (kappa=0.84–0.87, p<0.001) and weak to moderate agreement between rural doctors and the reference (kappa=0.48–0.64, p<0.001).ConclusionThis is the first study of diagnostic accuracy in DR grading among non-medical graders or ophthalmologists in low-income and middle-income countries. Non-medical graders can achieve high levels of accuracy, whereas accuracy of trained rural ophthalmologists is not optimal.
Management patterns of gastric polyps in the United States
Authors: Corral Juan E , Keihanian Tara , Diaz Liege I , Morgan Douglas R , Sussman Daniel A 
Published: July 2018

ObjectiveRecent guidelines on endoscopic sampling recommend complete gastric polyp removal for solitary fundic polyps >10 mm, hyperplastic polyps >5 mm and all adenomatous polyps. We aim to describe endoscopic approach to polyps in the time period prior to the American Society of Gastrointestinal Endoscopy (ASGE) guidelines and to identify opportunities for clinical practice improvements.DesignRetrospective review of the Clinical Outcome Research Initiative (CORI) database, including all oesophagogastroduodenoscopies (OGDs). Reviewers grouped interventions during procedures based on instruments used for polyp sampling by forceps or snare polypectomy. Logistic regression estimated the effect of variables of interest on method of polypectomy.ResultsOf 783 037 OGDs reported in the CORI database, 25 670 (3.3%) described gastric polyps and met the inclusion criteria. Mean gastric polyp size was 6.5±4.9 mm, and 46.2% and 14.5% were located in the corpus and antrum, respectively. Polyps in the forceps group were smaller than polyps in the snare group (5.7±4.0 mm vs 9.3±6.4 mm, respectively, p<0.001). We identified 1056 polyps (41.3%) >10 mm that only underwent forceps biopsy. Forceps were used more frequently in the gastric fundus.ConclusionsSnare polypectomy was underused in gastric polyps, per current ASGE guidelines. Anatomical location and endoscopic features of polyps were important predictors of the approach to gastric polypectomy.
Prognostic power of cardiopulmonary exercise testing in Fontan patients: a systematic review
Authors: Udholm Sebastian , Aldweib Nael , Hjortdal Vibeke Elisabeth , Veldtman Gruschen R 
Published: July 2018

ObjectiveExercise impairment is common in Fontan patients. Our aim is to systematically review previous literature to determine the prognostic value of exercise capacity in older adolescent and adult Fontan patients with respect to late outcome. Additionally, we reviewed the determinants of exercise capacity in Fontan patients and changes in exercise capacity over time.MethodsPubMed, CINAHL, Embase, The Cochrane Library and Scopus were searched systematically for studies reporting exercise capacity and late outcome such as mortality, cardiac transplantation and hospitalisation. Studies were eligible for inclusion if more than 30 patients were included and mean age was ≥16 years.ResultsFour thousand and seven hundred and twenty-two studies were identified by the systematic search. Seven studies fulfilled the inclusion and exclusion criteria. The total number of patients was 1664 adult Fontan patients. There were 149 deaths and 35 heart transplantations. All eligible studies were retrospective cohort studies. The correlation between exercise capacity and late outcome was identified, and HRs were reported.ConclusionIn Fontan patients, the best predictors of death and transplantation were a decline in peak VO2, heart rate variables and exercise oscillatory ventilation. Peak VO2was not strongly predictive of mortality or hospitalisation in Fontan patients. Several variables were strong and independent predictors of hospitalisation and morbidity.
Study on integration of aluminum-doped zinc oxide (AZO) thin films with graphene oxide (GO)
Authors: Dalal Aditya , Mandal Animesh , Adhi Shubhada , Adhi Kiran 
Published: July 2018

Aluminum (0.5 at.%)-doped ZnO (AZO) thin films were deposited by pulsed laser deposition technique (PLD) in oxygen ambient of 10[Formula: see text] Torr. The deposited thin films were characterized by x-ray diffraction (XRD), photoluminescence (PL), Raman spectroscopy and uv–visible spectroscopy (UV–vis). Next, graphene oxide (GO) was synthesized by Hummers method and was characterized by XRD, UV–vis spectroscopy, Raman spectroscopy and transmission electron microscopy (TEM). Thereafter, GO solution was drop-casted on AZO thin films. These films were then characterized by Raman Spectroscopy, UV–vis spectroscopy and PL. Attempt is being made to comprehend the modifications in properties brought about by integration.
Sn–3.0Ag–0.5Cu solder with minor added Ge and Pd–Cu reaction
Authors: Guo Y. Z. , Yan J. Y. , Yen Y. W. , Chu T. N. 
Published: July 2018

To improve solder-joint reliability, the Sn–3.0Ag–0.5Cu (SAC) solder had minor Ge and Pd additions to form composite solders. The results indicated that the Cu6Sn5 and Cu3Sn phases formed at the SAC–[Formula: see text]Ge/Cu interface ([Formula: see text], 0.5, 1.0, 2.0 wt.%) and the Ag3Sn phase precipitated in the solder. Cu6Sn5 and Cu3Sn phases formed at the interface and PdSn4 phase in the solder when the SAC–1.0Pd and SAC–2.0Pd reacted with the Cu. The SAC–1.0 Pd solder had the lowest liquidus temperature, and Ge addition improved the wettability.
Enhancement in field emission of MoS2 nanosheets prepared in water using laser ablation method
Authors: Kanazawa Makoto , Koinkar Pankaj , Furube Akihiro , Gavhane Dnyaneshwar , More Mahendra A. 
Published: July 2018

The laser ablation of a noble target material in a liquid is known as an alternative physical method for nanostructure fabrication. In the present study, the nanosecond laser ablation is used to irradiate MoS2 in water to produce MoS2 nanosheets. The experiments of laser ablation time of 20 minutes and 120 minutes have been carried out to study their field emission properties. Transmission electron microscopy (TEM) and Raman spectroscopy have been used to reveal surface and structural morphology. It is observed that the laser ablation time is an important factor in determining the size of MoS2 nanostructure. The Raman spectra of laser ablation confirm the formation of MoS2 nanosheets and removal of molybdenum oxide species. The TEM shows the size of MoS2 microsheet has been reduced from 2 [Formula: see text]m to 400 nm after the laser ablation treatment. It is found that the turn-on fields are reduced and current densities of MoS2 are increased after the laser ablation. The enhancement in the field emission characteristics of MoS2 is due to the reduction in the size of MoS2 and removal of molybdenum oxide species. The nanostructures produced by laser ablation may be used for optoelectronic application.
Cyanidin Protects SH-SY5Y Human Neuroblastoma Cells from 1-Methyl-4-Phenylpyridinium-Induced Neurotoxicity
Authors: Chen Jian , Sun Jian , Jiang Julian , Zhou Jie 
Published: July 2018

Cyanidin is an anthocyanidin extracted from a variety of fruits and vegetables. Cyanidin showed benefits against diabetes, cancer, and atherosclerosis. However, the potential neuroprotective effects of cyanidin against Parkinson’s disease (PD) have not been examined. Indicated concentrations of cyanidin (1, 3, 10, and 30 μmol/L) were incubated together with 0.5 mmol/L 1-methyl-4-phenylpyridinium (MPP+) to human neuroblastoma SH-SY5Y cells. We found cyanidin prevented MPP+-induced cell demise in a concentration-dependent manner. Cyanidin significantly reduced MPP+-induced apoptosis, this is reflected by decreased TdT-mediated dUTP nick-end labeling staining and caspase-3 expressions. Further, MPP+ increased the Bax/Bcl-2 ratio, which was partly reversed by cyanidin. We also found cyanidin attenuated the MPP+-induced mitochondrial oxidative stress as revealed by decreased MitoSOX staining. Taken together, these data for the first time indicated the ­neuroprotective effects of cyanidin against MPP+-induced ­SH-SY5Y cell death. These findings shed light on the potential implications of cyanidin for PD treatment.
Diversity and the Principle of Independence and Impartiality in the Future Multilateral Investment Court
Authors: Gómez Katia Fach 
Published: July 2018

Abstract
This article starts from the assumption that the future Multilateral Investment Court (MIC) will be shaped by a new and different type of international investment adjudicator (IIA) and focuses on the diversity issues that will need to be addressed during the Court’s creation. In this article, diversity is understood in a broad sense that includes questions related to IIA gender, race, geographical origins and legal background. The article argues that diversity may in fact evolve into one of the MIC’s key collective composition rules. It also sets out some of the grounds in favour of diversity in the MIC, and considers the specific ways in which diversity may permeate the constituent process for the MIC roster and its subsequent modus operandi. A further common thread is provided by the links between diversity and the principle of independence and impartiality, which will be a crucial MIC duty.
The International Investment Arbitrator’s Duty to Apply the Law
Authors: Karton Joshua 
Published: July 2018

Abstract
This article explores the sources, nature, and implications of an arbitrator’s duty to decide according to the governing law in investor-state arbitrations. It advances a contractarian conception of arbitral authority in investor-state arbitration, whereby the agreement of the states parties to the investment treaty is the source of both the arbitrator’s power to make decisions and the primary constraint on that power: the duty to apply the law. It argues that the choice of law provisions in investment treaties have a constitutional character for arbitral tribunals, such that a failure to apply the chosen law constitutes an excess of the tribunal’s powers which, if manifest, justifies annulment or non-enforcement of the award. The article concludes by considering the implications of this contractarian theory of arbitral powers and duties for arbitrators, disputing parties, and states seeking to reassert control over the investor-state dispute settlement system.