bluuebunny/crossref_metadata_2025 huggingface dataset:
Early germinal vesicle breakdown is a predictor of high preimplantation developmental competent oocytes in mice
Authors: Higaki Shogo , Kishi Masao , Koyama Keisuke , Nagano Masashi , Katagiri Seiji , Takada Tatsuyuki , Takahashi Yoshiyuki
Published: November 2016

The preselection of highly developmentally competent oocytes forin vitromaturation (IVM) is crucial for improving assisted reproductive technology. Although several intrinsic markers of oocyte quality are known to be closely related to the onset of nuclear maturation (germinal vesicle break down, GVBD), a direct comparison between GVBD timing and oocyte quality has never been reported. In this study, we established a non-invasive oocyte evaluation method based on GVBD timing for preselecting more developmental competent oocytes in mice. Because the O2concentration during IVM may affect the nuclear kinetics, all experiments were performed under two distinct O2concentrations: 20% and 5% O2. First, we determined the time course of changes in nuclear maturation and preimplantation developmental competence ofin vitro-matured oocytes to estimate GVBD timing in high developmental competent oocytes. Two-thirds of oocytes that underwent GVBD in early IVM seemed to mainly contribute to the blastocyst yield. To confirm this result, we compared the preimplantation developmental competence of the early and late GVBD oocytes. Cleavage and blastocyst formation rates of early GVBD oocytes (80.2% and 52.7% under 20% O2, respectively, and 67.6% and 47.3% under 5% O2, respectively) were almost double those of late GVBD oocytes (44.8% and 26.0% under 20% O2, respectively, and 40.4% and 17.9% under 5% O2, respectively). With no observable alterations by checking the timing of GVBD in preimplantation developmental competence, oocyte evaluation based on GVBD timing can be used as an efficient and non-invasive preselection method for high developmental competent oocytes.
THE DIVERSITY OF INTEGRATION IN A MULTIETHNIC METROPOLIS
Authors: Krysan Maria , Carter Courtney , van Londen Marieke
Published: November 2016

Although there is little debate that Census data reveal declines in standard measures of segregation over the past several decades, depending on who you ask, racial residential segregation is either just about gone or is stubbornly persistent. In this study, we draw attention to how the murkiness in the conceptualization of what has replaced ‘segregation’ and the related question of what integration is, contributes to this disagreement. Through an analysis of attitudes toward racially integrated neighborhoods, we demonstrate the pitfalls of our lack of consistency and clarity about the conceptual and operational definition of integration. Our analysis reveals the diversity of attitudes toward integrated communities—depending on who is asked, and what kind of integration is considered—and points to a fragility of commitment to the ideals of integration. We do this by using an innovative survey dataset that includes both open and closed-ended questions asked of a large probability sample of Whites, African Americans, and Latinos living in the Chicago metropolitan area. The survey asked individuals to describe their ideal neighborhood racial/ethnic composition and explain why it was ideal; they were then asked to describe (and explain) their least desired neighborhood racial/ethnic composition. Juxtaposing the results, we reveal that integration is both enthusiastically endorsed and much maligned—even within the same person—and that whether it is good or bad very much depends on the type of integration. We argue that appreciating the diversity of integration attitudes is critical if we are to develop a more nuanced understanding of future patterns of residential stratification in our increasingly diverse nation.
The determinants of defensive medicine practices in Belgium
Authors: Vandersteegen Tom , Marneffe Wim , Cleemput Irina , Vandijck Dominique , Vereeck Lode
Published: November 2016

In 2010 the Belgian government introduced a low cost administrative procedure for compensating medical injuries to overcome the major shortcomings of the existing tort system. This paper examines, for the first time, to what extent this reform had an impact on physician specialists’ defensive practices and what are the relevant determinants affecting physicians’ clinical decision making. Based on a survey of 508 physicians, we find evidence of a relatively modest increase in defensive practices among physicians in various specialties. In general, 14% of the respondents, who were aware of the reform, reported to have increased their overall defensive behaviour, while respectively 18 and 13% altered their assurance and avoidance behaviour. Commonly used physician characteristics, such as claims experience and gender, have a similar impact on defensive medicine as documented in existing literature. Furthermore, the determinant physician’s access to an incident reporting system is found to have a significant impact on most of the defensive medicine measures. Health care institutions may therefore play an important role in controlling and reducing physicians’ defensive practices.
Validation of the Maslach Burnout Inventory-General Survey on a Representative Sample of Dominican Teachers: Normative Data
Authors: Tomás José M. , de los Santos Saturnino , Alonso-Andres Alicia , Fernández Irene
Published: November 2016

Burnout is characterized by emotional exhaustion, depersonalization and lack of personal accomplishment (Bakke, Demerouti, & Sanz-Vergel, 2014). Several instruments for its measurement exist, but the most widely used scale for measuring its dimensions, by far, is the Maslach Burnout Inventory (MBI) in its different versions. Among the available versions of the scale, the MBI-General Survey was developed to measure three dimensions of burnout (cynicism, personal accomplishment, and emotional exhaustion) regardless of the type of work. The aim of this research is to offer evidence on the psychometric properties of the MBI-GS for its use in the Dominican Republic and other Caribbean Spanish-speaking countries, using representative sample of Dominican teachers. The factorial validity was studied through confirmatory factor analysis. Several competing models were proved in order to test the dimensionality of the scale. The confirmatory analyses shown that the original three-factor structure had a superior fit, but item eleven was removed in order to get an excellent fit χ2(87) = 211.19,p< .001, CFI = .98, RMSEA = .038 90% CI [.032–.045]. Regarding internal consistency, the CRI´s are well above the cut-off criteria of .7 (CRI’s ranged from .74 to .86). Concerning criterion-related validity, the three factors were correlated in the expected direction. Professional efficacy, a dimension of burnout measured in the opposite direction, was positively correlated with the three factors of work engagement, also as expected. This version was found to be a psychometrically sound measure of the three core dimensions of burnout.
Key to the Indies: Port Towns in the Spanish Caribbean: 1493–1550
Authors: Altman Ida
Published: November 2016

Seaborne commerce, communication, and transportation to a great extent defined and enabled the Spanish enterprise in the Caribbean from the time Europeans first arrived in the islands. With the exception of a minority of towns such as Concepción de la Vega in Española that were established in the interiors of the islands to provide access to gold mines and the indigenous labor to exploit them, the majority of new towns and cities were located on the coasts. Although Santo Domingo, San Juan, and eventually Havana emerged as the principal ports and administrative capitals of the large islands of the northern Caribbean in the first half of the sixteenth century, many secondary and small port towns played essential roles in the rapid development of systems of local and regional exchange, indigenous slave raiding, and transatlantic commerce that linked the islands to Seville, the Canaries and other islands of the Atlantic and the southern Caribbean. Allowing island residents to take advantage of waterborne transportation often via indigenous-built canoes, linking the islands to one another and the circum-Caribbean mainland, and serving as staging grounds for slave-raiding and other expeditions that radiated out from the islands, these towns helped to forge a diverse and dynamic region that was closely tied both to Spain and later to the developing societies of Spanish America.
Registry and health insurance claims data in vascular research and quality improvement
Authors: Behrendt Christian-Alexander , Heidemann Franziska , Rieß Henrik Christian , Stoberock Konstanze , Debus Sebastian Eike
Published: November 2016

Abstract. The expansion of procedures in multidisciplinary vascular medicine has sparked a controversy regarding measures of quality improvement. In addition to primary registries, the use of health insurance claims data is becoming of increasing importance. However, due to the fact that health insurance claims data are not collected for scientific evaluation but rather for reimbursement purposes, meticulous validation is necessary before and during usage in research and quality improvement matters. This review highlights the advantages and disadvantages of such data sources. A recent comprehensive expert opinion panel examined the use of health insurance claims data and other administrative data sources in medicine. Results from several studies concerning the validity of administrative data varied significantly. Validity of these data sources depends on the clinical relevance of the diagnoses considered. The rate of implausible information was 0.04 %, while the validity of the considered diagnoses varied between 80 and 97 % across multiple validation studies. A matching study between health insurance claims data of the third-largest German health insurance provider, DAK-Gesundheit, and a prospective primary registry of the German Society for Vascular Surgery demonstrated a good level of validity regarding the mortality of endovascular and open surgical treatment of abdominal aortic aneurysm in German hospitals. In addition, a large-scale international comparison of administrative data for the same disorder presented important results in treatment reality, which differed from those from earlier randomized controlled trials. The importance of administrative data for research and quality improvement will continue to increase in the future. When discussing the internal and external validity of this data source, one has to distinguish not only between its intended usage (research vs. quality improvement), but also between the included diseases and/or treatment procedures. Linkage between primary registry data and administrative data could be a reasonable solution to some current major issues of validity.
Does a TV Public Service Advertisement Campaign for Suicide Prevention Really Work?
Authors: Song In Han , You Jung-Won , Kim Ji Eun , Kim Jung-Soo , Kwon Se Won , Park Jong-Ik
Published: November 2016

Abstract. Background: One of the critical measures in suicide prevention is promoting public awareness of crisis hotline numbers so that individuals can more readily seek help in a time of crisis. Although public service advertisements (PSA) may be effective in raising the rates of both awareness and use of a suicide hotline, few investigations have been performed regarding their effectiveness in South Korea, where the suicide rate is the highest among OECD countries. Aims: The goal of this study was to evaluate the effectiveness of a television PSA campaign. Method: We analyzed a database of crisis phone calls compiled by the Korean Ministry of Health and Welfare to track changes in call volume to a crisis hotline that was promoted in a TV campaign. We compared daily call counts for three periods of equal length: before, during, and after the campaign. Results: The number of crisis calls during the campaign was about 1.6 times greater than the number before or after the campaign. Relative to the number of suicide-related calls in the previous year, the number of calls during the campaign period surged, displaying a noticeable increase. Conclusion: The findings confirmed that this campaign had a positive impact on call volume to the suicide hotline.
Largest Ever U.S. Shale Oil Deposit Identified in Texas
Authors: Sidder Aaron
Published: November 2016

The Wolfcamp shale, which underlies a large swath of Texas roughly centered on the city of Midland, contains 20 billion barrels of oil that could be recovered with current technology.
An intrinsic agonist mechanism for activation of glucagon-like peptide-1 receptor by its extracellular domain
Authors: Yin Yanting , Zhou X Edward , Hou Li , Zhao Li-Hua , Liu Bo , Wang Gaihong , Jiang Yi , Melcher Karsten , Xu H Eric
Published: November 2016

The glucagon-like peptide-1 receptor is a class B G protein coupled receptor (GPCR) that plays key roles in glucose metabolism and is a major therapeutic target for diabetes. The classic two-domain model for class B GPCR activation proposes that the apo-state receptor is auto-inhibited by its extracellular domain, which physically interacts with the transmembrane domain. The binding of the C-terminus of the peptide hormone to the extracellular domain allows the N-terminus of the hormone to insert into the transmembrane domain to induce receptor activation. In contrast to this model, here we demonstrate that glucagon-like peptide-1 receptor can be activated by N-terminally truncated glucagon-like peptide-1 or exendin-4 when fused to the receptor, raising the question regarding the role of N-terminal residues of peptide hormone in glucagon-like peptide-1 receptor activation. Mutations of cysteine 347 to lysine or arginine in intracellular loop 3 transform the receptor into a G protein-biased receptor and allow it to be activated by a nonspecific five-residue linker that is completely devoid of exendin-4 or glucagon-like peptide-1 sequence but still requires the presence of an intact extracellular domain. Moreover, the extracellular domain can activate the receptor in trans in the presence of an intact peptide hormone, and specific mutations in three extracellular loops abolished this extracellular domain trans-activation. Together, our data reveal a dominant role of the extracellular domain in glucagon-like peptide-1 receptor activation and support an intrinsic agonist model of the extracellular domain, in which peptide binding switches the receptor from the auto-inhibited state to the auto-activated state by releasing the intrinsic agonist activity of the extracellular domain.
Metabolic sialic acid blockade lowers the activation threshold of moDCs for TLR stimulation
Authors: Büll Christian , Collado‐Camps Estel , Kers‐Rebel Esther D , Heise Torben , Søndergaard Jonas N , den Brok Martijn H , Schulte Barbara M , Boltje Thomas J , Adema Gosse J
Published: November 2016

Sialic acid sugars cover the surface of dendritic cells (DCs) and have been suggested to impact several aspects of DC biology. Research into the role of sialic acids in DCs, however, is complicated by the limited number of tools available to modulate sialic acid expression. Here we report on a synthetic, fluorinated sialic acid mimetic, Ac53FaxNeu5Ac, which potently blocks sialic acid expression in human monocyte‐derived DCs (moDCs). Sialic acid blockade enhanced the responsiveness of moDCs to Toll‐like receptor (TLR) stimulation as measured by increased maturation marker expression and cytokine production. Consequently, the T‐cell activation capacity of Ac53FaxNeu5Ac‐treated moDCs was strongly increased. In addition to sialic acids, moDCs also expressed the sialic acid‐binding immunoglobulin‐like lectins (Siglecs) ‐3, ‐5, ‐7, ‐9 and ‐10, immune inhibitory receptors recognizing these sialic acids. Treatment with Ac53FaxNeu5Ac abrogated putative cis and trans interactions between sialic acids and Siglec‐7/‐9. Together, these data indicate that sialic acids limit the activation of moDCs via the TLR pathway, potentially by interacting with Siglec‐7 or Siglec‐9. Metabolic sialic acid blockade with Ac53FaxNeu5Ac could therefore potentially be used to generate more potent DC‐based vaccines for induction of robust anti‐viral or anti‐tumor immune responses.
Phase transformation strengthening of high-temperature superalloys
Authors: Smith T. M. , Esser B. D. , Antolin N. , Carlsson A. , Williams R. E. A. , Wessman A. , Hanlon T. , Fraser H. L. , Windl W. , McComb D. W. , Mills M. J.
Published: November 2016

Decades of research has been focused on improving the high-temperature properties of nickel-based superalloys, an essential class of materials used in the hot section of jet turbine engines, allowing increased engine efficiency and reduced CO2 emissions. Here we introduce a new ‘phase-transformation strengthening’ mechanism that resists high-temperature creep deformation in nickel-based superalloys, where specific alloying elements inhibit the deleterious deformation mode of nanotwinning at temperatures above 700 °C. Ultra-high-resolution structure and composition analysis via scanning transmission electron microscopy, combined with density functional theory calculations, reveals that a superalloy with higher concentrations of the elements titanium, tantalum and niobium encourage a shear-induced solid-state transformation from the γ′ to η phase along stacking faults in γ′ precipitates, which would normally be the precursors of deformation twins. This nanoscale η phase creates a low-energy structure that inhibits thickening of stacking faults into twins, leading to significant improvement in creep properties.
Inhibition of glycine transporter-1 in the dorsal vagal complex improves metabolic homeostasis in diabetes and obesity
Authors: Yue Jessica T. Y. , Abraham Mona A. , Bauer Paige V. , LaPierre Mary P. , Wang Peili , Duca Frank A. , Filippi Beatrice M. , Chan Owen , Lam Tony K. T.
Published: November 2016

Impaired glucose homeostasis and energy balance are integral to the pathophysiology of diabetes and obesity. Here we show that administration of a glycine transporter 1 (GlyT1) inhibitor, or molecular GlyT1 knockdown, in the dorsal vagal complex (DVC) suppresses glucose production, increases glucose tolerance and reduces food intake and body weight gain in healthy, obese and diabetic rats. These findings provide proof of concept that GlyT1 inhibition in the brain improves glucose and energy homeostasis. Considering the clinical safety and efficacy of GlyT1 inhibitors in raising glycine levels in clinical trials for schizophrenia, we propose that GlyT1 inhibitors have the potential to be repurposed as a treatment of both obesity and diabetes.
Modified relaxation dynamics and coherent energy exchange in coupled vibration-cavity polaritons
Authors: Dunkelberger A. D. , Spann B. T. , Fears K. P. , Simpkins B. S. , Owrutsky J. C.
Published: November 2016

Coupling vibrational transitions to resonant optical modes creates vibrational polaritons shifted from the uncoupled molecular resonances and provides a convenient way to modify the energetics of molecular vibrations. This approach is a viable method to explore controlling chemical reactivity. In this work, we report pump–probe infrared spectroscopy of the cavity-coupled C–O stretching band of W(CO)6 and the direct measurement of the lifetime of a vibration-cavity polariton. The upper polariton relaxes 10 times more quickly than the uncoupled vibrational mode. Tuning the polariton energy changes the polariton transient spectra and relaxation times. We also observe quantum beats, so-called vacuum Rabi oscillations, between the upper and lower vibration-cavity polaritons. In addition to establishing that coupling to an optical cavity modifies the energy-transfer dynamics of the coupled molecules, this work points out the possibility of systematic and predictive modification of the excited-state kinetics of vibration-cavity polariton systems.
Nanomechanical electro-optical modulator based on atomic heterostructures
Authors: Thomas P. A. , Marshall O. P. , Rodriguez F. J. , Auton G. H. , Kravets V. G. , Kundys D. , Su Y. , Grigorenko A. N.
Published: November 2016

Two-dimensional atomic heterostructures combined with metallic nanostructures allow one to realize strong light–matter interactions. Metallic nanostructures possess plasmonic resonances that can be modulated by graphene gating. In particular, spectrally narrow plasmon resonances potentially allow for very high graphene-enabled modulation depth. However, the modulation depths achieved with this approach have so far been low and the modulation wavelength range limited. Here we demonstrate a device in which a graphene/hexagonal boron nitride heterostructure is suspended over a gold nanostripe array. A gate voltage across these devices alters the location of the two-dimensional crystals, creating strong optical modulation of its reflection spectra at multiple wavelengths: in ultraviolet Fabry–Perot resonances, in visible and near-infrared diffraction-coupled plasmonic resonances and in the mid-infrared range of hexagonal boron nitride’s upper Reststrahlen band. Devices can be extremely subwavelength in thickness and exhibit compact and truly broadband modulation of optical signals using heterostructures of two-dimensional materials.
Evidence from stable isotopes and 10Be for solar system formation triggered by a low-mass supernova
Authors: Banerjee Projjwal , Qian Yong-Zhong , Heger Alexander , Haxton W C
Published: November 2016

About 4.6 billion years ago, some event disturbed a cloud of gas and dust, triggering the gravitational collapse that led to the formation of the solar system. A core-collapse supernova, whose shock wave is capable of compressing such a cloud, is an obvious candidate for the initiating event. This hypothesis can be tested because supernovae also produce telltale patterns of short-lived radionuclides, which would be preserved today as isotopic anomalies. Previous studies of the forensic evidence have been inconclusive, finding a pattern of isotopes differing from that produced in conventional supernova models. Here we argue that these difficulties either do not arise or are mitigated if the initiating supernova was a special type, low in mass and explosion energy. Key to our conclusion is the demonstration that short-lived 10Be can be readily synthesized in such supernovae by neutrino interactions, while anomalies in stable isotopes are suppressed.
Three-dimensional label-free imaging and quantification of lipid droplets in live hepatocytes
Authors: Kim Kyoohyun , Lee SeoEun , Yoon Jonghee , Heo JiHan , Choi Chulhee , Park YongKeun
Published: November 2016

Lipid droplets (LDs) are subcellular organelles with important roles in lipid storage and metabolism and involved in various diseases including cancer, obesity, and diabetes. Conventional methods, however, have limited ability to provide quantitative information on individual LDs and have limited capability for three-dimensional (3-D) imaging of LDs in live cells especially for fast acquisition of 3-D dynamics. Here, we present an optical method based on 3-D quantitative phase imaging to measure the 3-D structural distribution and biochemical parameters (concentration and dry mass) of individual LDs in live cells without using exogenous labelling agents. The biochemical change of LDs under oleic acid treatment was quantitatively investigated, and 4-D tracking of the fast dynamics of LDs revealed the intracellular transport of LDs in live cells.
Molecular mechanism of carbon nanotube to activate Subtilisin Carlsberg in polar and non-polar organic media
Authors: Zhang Liyun , Li Yuzhi , Yuan Yuan , Jiang Yuanyuan , Guo Yanzhi , Li Menglong , Pu Xuemei
Published: November 2016

In the work, we mainly used molecular dynamics (MD) simulation and protein structure network (PSN) to study subtilisin Carlsberg (SC) immobilized onto carbon nanotube (CNT) in water, acetonitrile and heptane solvents, in order to explore activation mechanism of enzymes in non-aqueous media. The result indicates that the affinity of SC with CNT follows the decreasing order of water > acetonitrile > heptane. The overall structure of SC and the catalytic triad display strong robustness to the change of environments, responsible for the activity retaining. However, the distances between two β-strands of substrate-binding pocket are significantly expanded by the immobilization in the increasing order of water < acetonitrile < heptane, contributing to the highest substrate-binding energy in heptane media. PSN analysis further reveals that the immobilization enhances structural communication paths to the substrate-binding pocket, leading to its larger change than the free-enzymes. Interestingly, the increase in the number of the pathways upon immobilization is not dependent on the absorbed extent but the desorbed one, indicating significant role of shifting process of experimental operations in influencing the functional region. In addition, some conserved and important hot-residues in the paths are identified, providing molecular information for functional modification.
Complex lasso: new entangled motifs in proteins
Authors: Niemyska Wanda , Dabrowski-Tumanski Pawel , Kadlof Michal , Haglund Ellinor , Sułkowski Piotr , Sulkowska Joanna I.
Published: November 2016

We identify new entangled motifs in proteins that we call complex lassos. Lassos arise in proteins with disulfide bridges (or in proteins with amide linkages), when termini of a protein backbone pierce through an auxiliary surface of minimal area, spanned on a covalent loop. We find that as much as 18% of all proteins with disulfide bridges in a non-redundant subset of PDB form complex lassos, and classify them into six distinct geometric classes, one of which resembles supercoiling known from DNA. Based on biological classification of proteins we find that lassos are much more common in viruses, plants and fungi than in other kingdoms of life. We also discuss how changes in the oxidation/reduction potential may affect the function of proteins with lassos. Lassos and associated surfaces of minimal area provide new, interesting and possessing many potential applications geometric characteristics not only of proteins, but also of other biomolecules.
Integrated omics study of lipid droplets from Plasmodiophora brassicae
Authors: Bi Kai , He Zhangchao , Gao Zhixiao , Zhao Ying , Fu Yanping , Cheng Jiasen , Xie Jiatao , Jiang Daohong , Chen Tao
Published: November 2016

Plasmodiophora brassicae causes clubroot disease in cruciferous. In this report, lipid droplets were observed in the resting spores of P. brassicae. 295 lipid droplet-associated proteins were identified and categorized into nine groups. Transcriptome analysis of these proteins during three different zoosporic stages revealed differences in gene expression pattern. GO enrichment analysis revealed that these proteins associated with lipid droplets were mainly linked to biosynthesis and metabolism. GC-MS analysis revealed that lipid droplets contain seven types of free fatty acids: saturated fatty acids C16:0 and C18:0, and unsaturated fatty acids C18:1Δ9, C18:1Δ11, C18:2, C20:4 and C20:5. P. brassicae accumulated a large amount of triacylglycerols (TAGs). We systematically analyzed the putative proteins involved in TAG biosynthesis and its metabolic pathway. KEGG pathway analysis defined 3390 genes, including 167 genes involved in lipid metabolism. Transcriptome analysis revealed that 162 candidate enzymes involved in lipid metabolism were differential expressed. Our omics studies are the first to investigate the lipid droplet organelles in P. brassicae, providing a reference resource to study protist lipid droplets.
Experience-Driven Differences in Childhood Cortisol Predict Affect-Relevant Brain Function and Coping in Adolescent Monozygotic Twins
Authors: Burghy Cory A. , Fox Michelle E. , Cornejo M. Daniela , Stodola Diane E. , Sommerfeldt Sasha L. , Westbrook Cecilia A. , Van Hulle Carol , Schmidt Nicole L. , Goldsmith H. Hill , Davidson Richard J. , Birn Rasmus M.
Published: November 2016

Stress and emotion involve diverse developmental and individual differences. Partially attributed to the development of the prefrontal cortex (PFC), the amygdala, and hypothalamic-pituitary-adrenal axis, the precise genetic and experiential contributions remain unknown. In previous work, childhood basal cortisol function predicted adolescent resting-state functional connectivity (rs-FC) and psychopathology. To parse experience-driven (non-genetic) contributions, we investigated these relations with a monozygotic (MZ) twin design. Specifically, we examined whether intrapair differences in childhood afternoon cortisol levels predicted cotwin differences in adolescent brain function and coping. As expected, intrapair differences in childhood cortisol forecast amygdala-perigenual PFC rs-FC (R2 = 0.84, FWE-corrected p = 0.01), and amygdala recovery following unpleasant images (R2 = 0.40, FWE-corrected p < 0.05), such that the cotwin with higher childhood cortisol evinced relatively lower rs-FC and poorer amygdala recovery in adolescence. Cotwin differences in amygdala recovery also predicted coping styles. These data highlight experience-dependent change in childhood and adolescence.
Targeted delivery system for cancer cells consist of multiple ligands conjugated genetically modified CCMV capsid on doxorubicin GNPs complex
Authors: Barwal Indu , Kumar Rajiv , Kateriya Suneel , Dinda Amit Kumar , Yadav Subhash Chandra
Published: November 2016

Targeted nano-delivery vehicles were developed from genetically modified Cowpea chlorotic mottle virus (CCMV) capsid by ligands bioconjugation for efficient drug delivery in cancer cells. RNA binding (N 1-25aa) and β-hexamer forming (N 27-41aa) domain of capsid was selectively deleted by genetic engineering to achieve the efficient in vitro assembly without natural cargo. Two variants of capsids were generated by truncating 41 and 26 amino acid from N terminus (NΔ41 and NΔ26) designated as F1 and F2 respectively. These capsid were optimally self-assembled in 1:2 molar ratio (F1:F2) to form a monodisperse nano-scaffold of size 28 nm along with chemically conjugated modalities for visualization (fluorescent dye), targeting (folic acid, FA) and anticancer drug (doxorubicin). The cavity of the nano-scaffold was packed with doxorubicin conjugated gold nanoparticles (10 nm) to enhance the stability, drug loading and sustained release of drug. The chimeric system was stable at pH range of 4–8. This chimeric nano-scaffold system showed highly specific receptor mediated internalization (targeting) and ~300% more cytotoxicity (with respect to FA− delivery system) to folate receptor positive Michigan Cancer Foundation-7 (MCF7) cell lines. The present system may offer a programmable nano-scaffold based platform for developing chemotherapeutics for cancer.
Association of pre-pregnancy body mass index, gestational weight gain with cesarean section in term deliveries of China
Authors: Xiong Chao , Zhou Aifen , Cao Zhongqiang , Zhang Yaqi , Qiu Lin , Yao Cong , Wang Youjie , Zhang Bin
Published: November 2016

China has one of the highest rates of cesarean sections in the world. However, limited epidemiological studies have evaluated the risk factors for cesarean section among Chinese women. Thus, the aim of this cohort study was to investigate the associations between pre-pregnancy BMI, gestational weight gain (GWG) and the risk of cesarean section in China. A total of 57,891 women with singleton, live-born, term pregnancies were included in this analysis. We found that women who were overweight or obese before pregnancy had an elevated risk of cesarean section. Women with a total GWG above the Institute of Medicine (IOM) recommendations had an adjusted OR for cesarean section of 1.45 (95% CI, 1.40–1.51) compared with women who had GWG within the IOM recommendations. Women with excessive BMI gain during pregnancy also had an increased risk of cesarean section. When stratified by maternal pre-pregnancy BMI, there was a significant association between excessive GWG and increased odds of cesarean section across all pre-pregnancy BMI categories. These results suggest that weight control efforts before and during pregnancy may help to reduce the rate of cesarean sections.
As-grown graphene/copper nanoparticles hybrid nanostructures for enhanced intensity and stability of surface plasmon resonance
Authors: Li Yun-Fei , Dong Feng-Xi , Chen Yang , Zhang Xu-Lin , Wang Lei , Bi Yan-Gang , Tian Zhen-Nan , Liu Yue-Feng , Feng Jing , Sun Hong-Bo
Published: November 2016

The transfer-free fabrication of the high quality graphene on the metallic nanostructures, which is highly desirable for device applications, remains a challenge. Here, we develop the transfer-free method by direct chemical vapor deposition of the graphene layers on copper (Cu) nanoparticles (NPs) to realize the hybrid nanostructures. The graphene as-grown on the Cu NPs permits full electric contact and strong interactions, which results in a strong localization of the field at the graphene/copper interface. An enhanced intensity of the localized surface plasmon resonances (LSPRs) supported by the hybrid nanostructures can be obtained, which induces a much enhanced fluorescent intensity from the dye coated hybrid nanostructures. Moreover, the graphene sheets covering completely and uniformly on the Cu NPs act as a passivation layer to protect the underlying metal surface from air oxidation. As a result, the stability of the LSPRs for the hybrid nanostructures is much enhanced compared to that of the bare Cu NPs. The transfer-free hybrid nanostructures with enhanced intensity and stability of the LSPRs will enable their much broader applications in photonics and optoelectronics.
Association of TNFSF4 Polymorphisms with Vogt-Koyanagi-Harada and Behcet’s Disease in Han Chinese
Authors: Lu Sha , Song Shengfang , Hou Shengping , Li Hua , Yang Peizeng
Published: November 2016

To investigate whether single nucleotide polymorphisms (SNPs) of the Tumor Necrosis Factor Superfamily 4 (TNFSF4) gene are associated with Vogt–Koyanagi–Harada (VKH) and Behcet’s disease (BD) in a Chinese Han population. A two-stage case control study was carried out in 1331 VKH, 938 BD and 1752 healthy controls. Ten TNFSF4 SNPs, including rs1234314, rs1234315, rs2205960, rs704840, rs2795288, rs844654, rs12039904, rs10912580, rs844665, and rs844644, were genotyped using the PCR-restriction fragment length polymorphism method. Genotype and allele frequencies were analyzed between cases and healthy controls using the X2 or Fisher’s exact test and p values were corrected for multiple comparisons. We observed a significantly increased frequency of the TT genotype of rs1234315 in BD patients (Pc = 1.44 × 10−5, OR = 1.734, 95% CI = 1.398–2.151). The frequency of the TT genotype of rs12039904 was significantly higher in patients with VKH disease as compared to controls (Pc = 4.62 × 10−5, OR = 1.959, 95% CI = 1.483–2.588). Analysis of clinical manifestations in VKH disease and BD did not show an association with the TNFSF4 gene polymorphisms. The study suggests that the TNFSF4 gene may be involved in the susceptibility to VKH disease and BD in Han Chinese.
A mouse model of hereditary hemorrhagic telangiectasia generated by transmammary-delivered immunoblocking of BMP9 and BMP10
Authors: Ruiz Santiago , Zhao Haitian , Chandakkar Pallavi , Chatterjee Prodyot K. , Papoin Julien , Blanc Lionel , Metz Christine N. , Campagne Fabien , Marambaud Philippe
Published: November 2016

Hereditary hemorrhagic telangiectasia (HHT) is a potentially life-threatening genetic vascular disorder caused by loss-of-function mutations in the genes encoding activin receptor-like kinase 1 (ALK1), endoglin, Smad4 and bone morphogenetic protein 9 (BMP9). Injections of mouse neonates with BMP9/10 blocking antibodies lead to HHT-like vascular defects in the postnatal retinal angiogenesis model. Mothers and their newborns share the same immunity through the transfer of maternal antibodies during lactation. Here, we investigated whether the transmammary delivery route could improve the ease and consistency of administering anti-BMP9/10 antibodies in the postnatal retinal angiogenesis model. We found that anti-BMP9/10 antibodies, when intraperitoneally injected into lactating dams, are efficiently transferred into the blood circulation of lactationally-exposed neonatal pups. Strikingly, pups receiving anti-BMP9/10 antibodies via lactation displayed consistent and robust vascular pathology in the retina, which included hypervascularization and defects in arteriovenous specification, as well as the presence of multiple and massive arteriovenous malformations. Furthermore, RNA-Seq analyses of neonatal retinas identified an increase in the key pro-angiogenic factor, angiopoietin-2, as the most significant change in gene expression triggered by the transmammary delivery of anti-BMP9/10 antibodies. Transmammary-delivered BMP9/10 immunoblocking in the mouse neonatal retina is therefore a practical, noninvasive, reliable and robust model of HHT vascular pathology.
Effects of light-emitting diode irradiation on the osteogenesis of human umbilical cord mesenchymal stem cells in vitro
Authors: Yang Dazhi , Yi Weihong , Wang Ertian , Wang Min
Published: November 2016

The aim of this study was to examine the effects of light-emitting diode (LED) photobiomodulation therapy on the proliferation and differentiation of human umbilical cord mesenchymal stem cells (hUMSCs) cultured in osteogenic differentiation medium. HUMSCs were irradiated with an LED light at 620 nm and 2 J/cm2 and monitored for cell proliferation and osteogenic differentiation activity. The experiment involved four groups of cells: the control group; the osteogenic group (osteo group); the LED group; the osteogenic + LED group (LED + osteo group). HUMSC proliferation was detected by performing a3-(4,5-dimethylthiazol-2yl)-2,5 diphenyltetrazolium bromide(MTT) assay. Osteogenic activity was evaluated by performing alkaline phosphatase (ALP) and Von Kossa staining, and osteopontin (OPN) gene mRNA expression was evaluated byreverse transcription polymerase chain reaction (RT-PCR). The hUMSCs in the LED + osteo group exhibited a significantly higher proliferation rate than the other subgroups. Additionally, there were greater numbers of ALP-positive cells and Von Kossa nodules in the LED + osteo group. OPN mRNA expression in the LED + osteo group was higher than other subgroups. In conclusion, low levels of LED light at a wavelength of 620 nm enhance the proliferation and osteogenic differentiation of hUMSCs during a long culture period.
Role of valence changes and nanoscale atomic displacements in BiS2-based superconductors
Authors: Cheng Jie , Zhai Huifei , Wang Yu , Xu Wei , Liu Shengli , Cao Guanghan
Published: November 2016

Superconductivity within layered crystal structures has attracted sustained interest among condensed matter community, primarily due to their exotic superconducting properties. EuBiS2F is a newly discovered member in the BiS2-based superconducting family, which shows superconductivity at 0.3 K without extrinsic doping. With 50 at.% Ce substitution for Eu, superconductivity is enhanced with Tc increased up to 2.2 K. However, the mechanisms for the Tc enhancement have not yet been elucidated. In this study, the Ce-doping effect on the self-electron-doped superconductor EuBiS2F was investigated by X-ray absorption spectroscopy (XAS). We have established a relationship between Ce-doping and the Tc enhancement in terms of Eu valence changes and nanoscale atomic displacements. The new finding sheds light on the interplay among superconductivity, charge and local structure in BiS2-based superconductors.
Loss-of-function of an Arabidopsis NADPH pyrophosphohydrolase, AtNUDX19, impacts on the pyridine nucleotides status and confers photooxidative stress tolerance
Authors: Maruta Takanori , Ogawa Takahisa , Tsujimura Masaki , Ikemoto Keisuke , Yoshida Tomofumi , Takahashi Hiro , Yoshimura Kazuya , Shigeoka Shigeru
Published: November 2016

The levels and redox states of pyridine nucleotides, such as NADP(H), regulate the cellular redox homeostasis, which is crucial for photooxidative stress response in plants. However, how they are controlled is poorly understood. AnArabidopsisNudix hydrolase, AtNUDX19, was previously identified to have NADPH hydrolytic activityin vitro, suggesting this enzyme to be a regulator of the NADPH status. We herein examined the physiological role of AtNUDX19 using its loss-of-function mutants. NADPH levels were increased innudx19mutants under both normal and high light conditions, while NADP+and NAD+levels were decreased. Despite the high redox states of NADP(H),nudx19mutants exhibited high tolerance to moderate light- or methylviologen-induced photooxidative stresses. This tolerance might be partially attributed to the activation of either or both photosynthesis and the antioxidant system. Furthermore, a microarray analysis suggested the role of ANUDX19 in regulation of the salicylic acid (SA) response in a negative manner. Indeed,nudx19mutants accumulated SA and showed high sensitivity to the hormone. Our findings demonstrate that ANUDX19 acts as an NADPH pyrophosphohydrolase to modulate cellular levels and redox states of pyridine nucleotides and fine-tunes photooxidative stress response through the regulation of photosynthesis, antioxidant system, and possibly hormonal signaling.
Second-trimester urine nephrin:creatinine ratio versus soluble fms-like tyrosine kinase-1:placental growth factor ratio for prediction of preeclampsia among asymptomatic women
Authors: Zhai Tianyue , Furuta Itsuko , Nakagawa Kinuko , Kojima Takashi , Umazume Takeshi , Ishikawa Satoshi , Yamada Takahiro , Morikawa Mamoru , Minakami Hisanori
Published: November 2016

This prospective observational study compare urine nephrin:creatinine ratio (NCR, ng/mg) with serum soluble fms-like tyrosine kinase-1:placental growth factor ratio (FPR, pg/pg) for preeclampsia (PE) prediction among unselected asymptomatic pregnant women in 2nd trimester. NCR and FPR were determined in 254 paired urine/blood samples collected simultaneously from 254 women at median gestational week (GW) 24 (range, 22–27) without hypertension or significant proteinuria in pregnancy (SPIP). Fifteen (5.9%) developed SPIP and hypertension at GW 34.0 (26.0–38.6) and 35.3 (27.6–38.6), respectively, and were diagnosed with PE at GW 35.7 (27.6–38.6). The 90th percentile level determined in 239 women normotensive throughout pregnancy gave NCR (139) sensitivity and positive predictive values (PPV) of 60% (9/15) and 27% (9/33), while those for serum FPR (4.85) were 40% (6/15) and 20% (6/30), respectively. Relative risks (95%CI) of later PE were 10.0 (3.82–26.4; 27% [9/33] vs. 2.7% [6/221]) and 4.98 (1.91–13.0; 20% [6/30] vs. 4.0% [9/224]) for NCR-positive and FPR-positive women, respectively. Cut-offs suggested by ROC gave NCR (86.6) sensitivity and PPV of 87% (13/15) and 17% (13/79), and FPR (8.8) values of 40% (6/15) and 40% (6/15), respectively. Thus, 2nd trimester NCR was superior to FPR for PE prediction.
Identifying mutations in Tunisian families with retinal dystrophy
Authors: Habibi Imen , Chebil Ahmed , Falfoul Yosra , Allaman-Pillet Nathalie , Kort Fedra , Schorderet Daniel F. , El Matri Leila
Published: November 2016

Retinal dystrophies (RD) are a rare genetic disorder with high genetic heterogeneity. This study aimed at identifying disease-causing variants in fifteen consanguineous Tunisian families. Full ophthalmic examination was performed. Index patients were subjected to IROme analysis or whole exome sequencing followed by homozygosity mapping. All detected variations were confirmed by direct Sanger sequencing. Mutation analysis in our patients revealed two compound heterozygous mutations p.(R91W);(V172D) in RPE65, and five novel homozygous mutations: p.R765C in CNGB1, p.H337R in PDE6B, splice site variant c.1129-2A > G and c.678_681delGAAG in FAM161A and c.1133 + 3_1133 + 6delAAGT in CERKL. The latter mutation impacts pre-mRNA splicing of CERKL. The other changes detected were six previously reported mutations in CNGB3 (p.R203*), ABCA4 (p.W782*), NR2E3 (p.R311Q), RPE65 (p.H182Y), PROM1 (c.1354dupT) and EYS (c.5928-2A > G). Segregation analysis in each family showed that all affected individuals were homozygotes and unaffected individuals were either heterozygote carriers or homozygous wild type allele. These results confirm the involvement of a large number of genes in RD in the Tunisian population.
Glutamate dehydrogenase activator BCH stimulating reductive amination prevents high fat/high fructose diet-induced steatohepatitis and hyperglycemia in C57BL/6J mice
Authors: Han Seung Jin , Choi Sung-E , Yi Sang-A , Jung Jong Gab , Jung Ik-Rak , Shin Maureen , Kang Seok , Oh Hyunhee , Kim Hae Jin , Kim Dae Jung , Kwon Ji Eun , Choi Cheol Soo , Lee Kwan Woo , Kang Yup
Published: November 2016

Individuals with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D) induced by high calorie western diet are characterized by enhanced lipogenesis and gluconeogenesis in the liver. Stimulation of reductive amination may shift tricarboxylic acid cycle metabolism for lipogenesis and gluconeogenesis toward glutamate synthesis with increase of NAD+/NADH ratio and thus, ameliorate high calorie diet-induced fatty liver and hyperglycemia. Stimulation of reductive amination through glutamate dehydrogenase (GDH) activator 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) reduced both de novo lipogenesis and gluconeogenesis but increased the activities of sirtuins and AMP-activated kinase in primary hepatocytes. Long-term BCH treatment improved most metabolic alterations induced by high fat/high fructose (HF/HFr) diet in C57BL/6J mice. BCH prevented HF/HFr-induced fat accumulation and activation of stress/inflammation signals such as phospho-JNK, phospho-PERK, phospho-p38 and phospho-NFκB in liver tissues. Furthermore, BCH treatment reduced the expression levels of inflammatory cytokines such as TNF-α and IL-1β in HF/HFr-fed mouse liver. BCH also reduced liver collagen and plasma levels of alanine transaminase and aspartate transaminase. On the other hand, BCH significantly improved fasting hyperglycemia and glucose tolerance in HF/HFr-fed mice. In conclusion, stimulation of reductive amination through GDH activation can be used as a strategy to prevent high calorie western diet-induced NAFLD and T2D.
Enterohemorrhagic Escherichia coli promotes the invasion and tissue damage of enterocytes infected with Candida albicans in vitro
Authors: Yang Weiming , Zhou Yanjun , Wu Chunrong , Tang Jianguo
Published: November 2016

The principal aim of this study was to investigate the in vitro co-infection of Caco-2 cells with Candida albicans and enterohemorrhage Escherichia coli (EHEC). The ability of both species to colonize or invade the Caco-2 cells was evaluated by indirect immunofluorescence and inverted microscopy. The damage to Caco-2 cells was evaluated by measuring lactate dehydrogenase (LDH) activity. C. albicans virulence gene expression (HWP1, ALS3, PLB1, SAP4, and EFG1) was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Compared to single infections with enterohemorrhage Escherichia coli or C. albicans, a co-infection colonized or invaded Caco-2 cells more quickly, and C. albicans tended to accumulate more easily, accompanied by the upregulation of related genes. In addition, the LDH activity in the co-infected group was higher than in cells infected with C. albicans or with enterohemorrhage Escherichia coli, accompanied by the upregulation of toxicity-related genes. Using Caco-2 cells as an infection model, this study demonstrated that co-infecting in vitro enterocytes with C. albicans and enterohemorrhage Escherichia coli enhanced the invasiveness and tissue damaging effects of C. albicans.