bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictors of IAPT psychological well-being practitioners’ intention to use CBT self-help materials routinely in their clinical practice
Authors: Levy Michelle A. , Holttum Sue , Dooley Jemima , Ononaiye Margo
Published: June 2016

Despite efficacy and effectiveness evidence, and recommendations from the National Institute for Health and Care Excellence (NICE), use of CBT self-help materials remains inconsistent in UK mental health services. Since 2006, the Improving Access to Psychological Therapies (IAPT) programme has provided standardized training and mandates routine use of CBT self-help materials by their trainee psychological well-being practitioners (PWPs). This study tested whether the main constructs of the theory of planned behaviour (TPB; attitudes, subjective norms, and perceived behavioural control), past use, prior training and demographic characteristics, would predict PWPs’ intention to use self-help materials routinely in their clinical practice. Stage 1 utilized a standardized procedure to create measures for the constructs of TPB, before the design and testing of a web-based, cross-sectional questionnaire. In stage 2, the questionnaire was administered to a convenience sample of trainee PWPs (n = 94). Data was analysed using multiple linear regression, mediation analyses, and content analysis. TPB constructs predicted intention to use self-help materials, with only direct attitude contributing significantly to 70% of the variance in intention. Past use of materials predicted intention, via direct and indirect mediation. Qualitative data from 43 trainees highlighted clients’ experience of self-help materials as positive, albeit with some practical constraints. The results suggest that the main constructs of TPB have some utility in predicting trainee PWPs’ intention to use self-help materials routinely. Future prospective, longitudinal research could investigate actual use of self-help materials to elucidate cognitive factors involved in trainees’ clinical decision-making post-qualification.
Development and Validation of the Gatekeeper Behavior Scale
Authors: Albright Glenn L. , Davidson Jesse , Goldman Ron , Shockley Kristen M. , Timmons-Mitchell Jane
Published: June 2016

Abstract. Background: Community-based gatekeeper trainings are effective tools in increasing gatekeeper skills but few validated measures assess impact. Aims: This study aimed at determining the validity of an 11-item Gatekeeper Behavior Scale (GBS) to assess gatekeeper skills that predict behavior. Method: To validate the scale, 8,931 users were administered GBS surveys at pretraining, posttraining, and follow-up periods. The training was one of five from the suite of online At-Risk mental health learning simulations for university faculty/staff or students or high/middle school educators. Results: A confirmatory factor analysis revealed the three-factor model based on the subscales of preparedness, likelihood, and self-efficacy fit the data best. Factor loadings showed all items correlated highly with theoretical constructs (r ≥ .84, p < .001). The GBS had high internal consistency (α = 0.93). Criterion-related validity for likelihood to discuss concerns at posttraining was significantly related to approaching students believed to be in psychological distress (r = .219, p < .001). Likelihood to refer significantly correlated with the number of students referred (r = .235, p < .001). Convergent validity was established via a correlation between self-efficacy in motivating someone to seek help and general self-efficacy (r = .519, p < .001). Conclusion: The GBS appears to be a valid tool in measuring the impact of online gatekeeper training simulations and holds promise for assessing other delivery methods.
Gender Differences in Youth Suicide and Healthcare Service Use
Authors: Gontijo Guerra Samantha , Vasiliadis Helen-Maria
Published: June 2016

Abstract. Background: Healthcare service use among suicide decedents must be well characterized and understood since a key strategy for preventing suicide is to improve healthcare providers' ability to effectively detect and treat those in need. Aims: To determine gender differences in healthcare service use 12 months prior to suicide. Method: Data for 1,231 young Quebec residents (≤ 25 years) who died by suicide between 2000 and 2007 were collected from public health insurance agency databases and coroner registers. Healthcare visits were categorized according to the setting (emergency department [ED], outpatient, and hospital) and their nature (mental health vs. non-mental health). Results: Girls were more likely than boys (82.5% vs. 74.9%, p = .011) to have used healthcare services in the year prior to death. A higher proportion of girls had used outpatient services (79.0% vs. 69.5%, p = .003), had been hospitalized (25.7% vs. 15.6%, p < .001) and had received a mental health-related diagnosis (46.7% vs. 33.1%, p < .001). However, no gender differences were observed in ED visits (59.5% vs. 54.5%, p = .150). Conclusion: There is an important proportion of suicide decedents who did not receive a mental health diagnosis and healthcare services in the year prior to death. Future studies should focus on examining gender-specific individual and health system barriers among suicide decedents as well as the quality of care offered regarding detection and treatment.
Benefits of a Secondary Prevention Program in Suicide
Authors: Farré Adriana , Portella Maria J. , De Angel Luis , Díaz Ana , de Diego-Adeliño Javier , Vegué Joan , Duran-Sindreu Santiago , Faus Gustavo , Tejedor Carmen , Álvarez Enric , Pérez Víctor
Published: June 2016

Abstract. Background: The effectiveness of suicide intervention programs has not been assessed with experimental designs. Aim: To determine the risk of suicide reattempts in patients engaged in a secondary prevention program. Method: We included 154 patients with suicidal behavior in a quasi-experimental study with a nontreatment concurrent control group. In all, 77 patients with suicidal behavior underwent the Suicide Behavior Prevention Program (SBPP), which includes specialized early assistance during a period of 3–6 months. A matched sample of patients with suicidal behavior (n = 77) was selected without undergoing any specific suicide prevention program. Data on sociodemographics, clinical characteristics, and suicidal behavior were collected at baseline (before SBPP) and at 12 months. Results: After 12 months, SBPP patients showed a 67% lower relative risk of reattempt (χ2 = 11.75, p = .001, RR = 0.33 95% CI = 0.17–0.66). Cox proportional hazards models revealed that patients under SBPP made a new suicidal attempt significantly much later than control patients did (Cox regression = 0.293, 95% CI = 0.138–0.624, p = .001). The effect was even stronger among first attempters. Limitations: Sampling was naturalistic and patients were not randomized. Conclusion: The SBPP was effective in delaying and preventing suicide reattempts at least within the first year after the suicide behavior. In light of our results, implementation of suicide prevention programs is strongly advisable.
The ubiquitin E3 ligase TRAF6 exacerbates pathological cardiac hypertrophy via TAK1-dependent signalling
Authors: Ji Yan-Xiao , Zhang Peng , Zhang Xiao-Jing , Zhao Yi-Chao , Deng Ke-Qiong , Jiang Xi , Wang Pi-Xiao , Huang Zan , Li Hongliang
Published: June 2016

Tumour necrosis factor receptor-associated factor 6 (TRAF6) is a ubiquitin E3 ligase that regulates important biological processes. However, the role of TRAF6 in cardiac hypertrophy remains unknown. Here, we show that TRAF6 levels are increased in human and murine hypertrophied hearts, which is regulated by reactive oxygen species (ROS) production. Cardiac-specific Traf6 overexpression exacerbates cardiac hypertrophy in response to pressure overload or angiotensin II (Ang II) challenge, whereas Traf6 deficiency causes an alleviated hypertrophic phenotype in mice. Mechanistically, we show that ROS, generated during hypertrophic progression, triggers TRAF6 auto-ubiquitination that facilitates recruitment of TAB2 and its binding to transforming growth factor beta-activated kinase 1 (TAK1), which, in turn, enables the direct TRAF6–TAK1 interaction and promotes TAK1 ubiquitination. The binding of TRAF6 to TAK1 and the induction of TAK1 ubiquitination and activation are indispensable for TRAF6-regulated cardiac remodelling. Taken together, we define TRAF6 as an essential molecular switch leading to cardiac hypertrophy in a TAK1-dependent manner.
Robust and stretchable indium gallium zinc oxide-based electronic textiles formed by cilia-assisted transfer printing
Authors: Yoon Jongwon , Jeong Yunkyung , Kim Heeje , Yoo Seonggwang , Jung Hoon Sun , Kim Yonghun , Hwang Youngkyu , Hyun Yujun , Hong Woong-Ki , Lee Byoung Hun , Choa Sung-Hoon , Ko Heung Cho
Published: June 2016

Electronic textile (e-textile) allows for high-end wearable electronic devices that provide easy access for carrying, handling and using. However, the related technology does not seem to be mature because the woven fabric hampers not only the device fabrication process directly on the complex surface but also the transfer printing of ultrathin planar electronic devices. Here we report an indirect method that enables conformal wrapping of surface with arbitrary yet complex shapes. Artificial cilia are introduced in the periphery of electronic devices as adhesive elements. The cilia also play an important role in confining a small amount of glue and damping mechanical stress to maintain robust electronic performance under mechanical deformation. The example of electronic applications depicts the feasibility of cilia for ‘stick-&-play’ systems, which provide electronic functions by transfer printing on unconventional complex surfaces.
Shaping nanoscale magnetic domain memory in exchange-coupled ferromagnets by field cooling
Authors: Chesnel Karine , Safsten Alex , Rytting Matthew , Fullerton Eric E.
Published: June 2016

The advance of magnetic nanotechnologies relies on detailed understanding of nanoscale magnetic mechanisms in materials. Magnetic domain memory (MDM), that is, the tendency for magnetic domains to repeat the same pattern during field cycling, is important for magnetic recording technologies. Here we demonstrate MDM in [Co/Pd]/IrMn films, using coherent X-ray scattering. Under illumination, the magnetic domains in [Co/Pd] produce a speckle pattern, a unique fingerprint of their nanoscale configuration. We measure MDM by cross-correlating speckle patterns throughout magnetization processes. When cooled below its blocking temperature, the film exhibits up to 100% MDM, induced by exchange-coupling with the underlying IrMn layer. The degree of MDM drastically depends on cooling conditions. If the film is cooled under moderate fields, MDM is high throughout the entire magnetization loop. If the film is cooled under nearly saturating field, MDM vanishes, except at nucleation and saturation. Our findings show how to fully control the occurrence of MDM by field cooling.
Conventional methanotrophs are responsible for atmospheric methane oxidation in paddy soils
Authors: Cai Yuanfeng , Zheng Yan , Bodelier Paul L. E. , Conrad Ralf , Jia Zhongjun
Published: June 2016

Soils serve as the biological sink of the potent greenhouse gas methane with exceptionally low concentrations of ∼1.84 p.p.m.v. in the atmosphere. The as-yet-uncultivated methane-consuming bacteria have long been proposed to be responsible for this ‘high-affinity’ methane oxidation (HAMO). Here we show an emerging HAMO activity arising from conventional methanotrophs in paddy soil. HAMO activity was quickly induced during the low-affinity oxidation of high-concentration methane. Activity was lost gradually over 2 weeks, but could be repeatedly regained by flush-feeding the soil with elevated methane. The induction of HAMO activity occurred only after the rapid growth of methanotrophic populations, and a metatranscriptome-wide association study suggests that the concurrent high- and low-affinity methane oxidation was catalysed by known methanotrophs rather than by the proposed novel atmospheric methane oxidizers. These results provide evidence of atmospheric methane uptake in periodically drained ecosystems that are typically considered to be a source of atmospheric methane.
Convulsive seizures from experimental focal cortical dysplasia occur independently of cell misplacement
Authors: Hsieh Lawrence S. , Wen John H. , Claycomb Kumiko , Huang Yuegao , Harrsch Felicia A. , Naegele Janice R. , Hyder Fahmeed , Buchanan Gordon F. , Bordey Angelique
Published: June 2016

Focal cortical dysplasia (FCD), a local malformation of cortical development, is the most common cause of pharmacoresistant epilepsy associated with life-long neurocognitive impairments. It remains unclear whether neuronal misplacement is required for seizure activity. Here we show that dyslamination and white matter heterotopia are not necessary for seizure generation in a murine model of type II FCDs. These experimental FCDs generated by increasing mTOR activity in layer 2/3 neurons of the medial prefrontal cortex are associated with tonic-clonic seizures and a normal survival rate. Preventing all FCD-related defects, including neuronal misplacement and dysmorphogenesis, with rapamycin treatments from birth eliminates seizures, but seizures recur after rapamycin withdrawal. In addition, bypassing neuronal misplacement and heterotopia using inducible vectors do not prevent seizure occurrence. Collectively, data obtained using our new experimental FCD-associated epilepsy suggest that life-long treatment to reduce neuronal dysmorphogenesis is required to suppress seizures in individuals with FCD.
In vivo modulation of endothelial polarization by Apelin receptor signalling
Authors: Kwon Hyouk-Bum , Wang Shengpeng , Helker Christian S. M. , Rasouli S. Javad , Maischein Hans-Martin , Offermanns Stefan , Herzog Wiebke , Stainier Didier Y. R.
Published: June 2016

Endothelial cells (ECs) respond to shear stress by aligning in the direction of flow. However, how ECs respond to flow in complex in vivo environments is less clear. Here we describe an endothelial-specific transgenic zebrafish line, whereby the Golgi apparatus is labelled to allow for in vivo analysis of endothelial polarization. We find that most ECs polarize within 4.5 h after the onset of vigorous blood flow and, by manipulating cardiac function, observe that flow-induced EC polarization is a dynamic and reversible process. Based on its role in EC migration, we analyse the role of Apelin signalling in EC polarization and find that it is critical for this process. Knocking down Apelin receptor function in human primary ECs also affects their polarization. Our study provides new tools to analyse the mechanisms of EC polarization in vivo and reveals an important role in this process for a signalling pathway implicated in cardiovascular disease.
Probing local and electronic structure in Warm Dense Matter: single pulse synchrotron x-ray absorption spectroscopy on shocked Fe
Authors: Torchio Raffaella , Occelli Florent , Mathon Olivier , Sollier Arnaud , Lescoute Emilien , Videau Laurent , Vinci Tommaso , Benuzzi-Mounaix Alessandra , Headspith Jon , Helsby William , Bland Simon , Eakins Daniel , Chapman David , Pascarelli Sakura , Loubeyre Paul
Published: June 2016

Understanding Warm Dense Matter (WDM), the state of planetary interiors, is a new frontier in scientific research. There exists very little experimental data probing WDM states at the atomic level to test current models and those performed up to now are limited in quality. Here, we report a proof-of-principle experiment that makes microscopic investigations of materials under dynamic compression easily accessible to users and with data quality close to that achievable at ambient. Using a single 100 ps synchrotron x-ray pulse, we have measured, by K-edge absorption spectroscopy, ns-lived equilibrium states of WDM Fe. Structural and electronic changes in Fe are clearly observed for the first time at such extreme conditions. The amplitude of the EXAFS oscillations persists up to 500 GPa and 17000 K, suggesting an enduring local order. Moreover, a discrepancy exists with respect to theoretical calculations in the value of the energy shift of the absorption onset and so this comparison should help to refine the approximations used in models.
Multiple host switching events shape the evolution of symbiotic palaemonid shrimps (Crustacea: Decapoda)
Authors: Horká Ivona , De Grave Sammy , Fransen Charles H. J. M. , Petrusek Adam , Ďuriš Zdeněk
Published: June 2016

The majority of the almost 1,000 species of Palaemonidae, the most speciose family of caridean shrimp, largely live in symbioses with marine invertebrates of different phyla. These associations range from weak epibiosis to obligatory endosymbiosis and from restricted commensalism to semi-parasitism, with the specialisation to particular hosts likely playing a role in the diversification of this shrimp group. Our study elucidates the evolutionary history of symbiotic palaemonids based on a phylogenetic analysis of 87 species belonging to 43 genera from the Indo-West Pacific and the Atlantic using two nuclear and two mitochondrial markers. A complementary three-marker analysis including taxa from GenBank raises this number to 107 species from 48 genera. Seven larger clades were recovered in the molecular phylogeny; the basal-most one includes mostly free-living shrimp, albeit with a few symbiotic species. Ancestral state reconstruction revealed that free-living forms likely colonised cnidarian hosts initially and switching between different host phyla occurred multiple times in palaemonid evolutionary history. In some cases this was likely facilitated by the availability of analogous microhabitats in unrelated but morphologically similar host groups. Host switching and adaptations to newly colonised host groups must have played an important role in the evolution of this diverse shrimp group.
Establishment and application of a real-time loop-mediated isothermal amplification system for the detection of CYP2C19 polymorphisms
Authors: Zhang Chao , Yao Yao , Zhu Juan-Li , Zhang Si-Nong , Zhang Shan-Shan , Wei Hua , Hui Wen-Li , Cui Ya-Li
Published: June 2016

Single-nucleotide polymorphisms (SNPs) represent the most widespread type of genetic variation (approximately 90%) in the human genome, and the demand to overcome such variation has received more attention now than ever before. The capacity to rapidly assess SNPs that correlate with disease predisposition, drug efficacy and drug toxicity is a key step for the development of personalized medicine. In this work, a rapid one-step SNP detection method, real-time loop-mediated isothermal amplification (RT-LAMP), was first applied for CYP2C19 polymorphisms testing. The optimized method was established with specifically designed primers for target amplification by real-time detection in approximately 30 min under isothermal conditions. RT-LAMP amplified few copies of template to produce significant amounts of product and quantitatively detected human DNA with compatible specificity and sensitivity. The success in the establishment of this RT-LAMP protocol for CYP2C19 polymorphism testing is significant for the extension of this technique for the detection of other SNPs, which will further facilitate the development of personalized medicine.
SCF/c-kit transactivates CXCR4-serine 339 phosphorylation through G protein-coupled receptor kinase 6 and regulates cardiac stem cell migration
Authors: Zuo Ke , Kuang Dong , Wang Ying , Xia Yanli , Tong Weilin , Wang Xiaoyan , Chen Yaobin , Duan Yaqi , Wang Guoping
Published: June 2016

C-kit positive cardiac stem cells (CSCs) have been shown to contribute to myocardial regeneration after infarction. Previously, we have shown that the c-kit ligand stem cell factor (SCF) can induce CSC migration into the infarcted area during myocardial infarction (MI). However, the precise mechanism involved is not fully understood. In this study, we found that CSCs also express C-X-C chemokine receptor type 4 (CXCR4), which is a typical member of the seven transmembrane-spanning G protein-coupled receptor (GPCR). In vitro, activation of c-kit signalling by SCF promotes migration of CSCs with increased phosphorylation of CXCR4-serine 339, p38 mitogen-activated protein kinase (p38 MAPK) and extracellular regulated protein kinases 1/2 (ERK1/2). Knockdown of CXCR4 expression by siRNA reduces SCF/c-kit-induced migration and downstream signalling. As previously reported, CXCR4-serine 339 phosphorylation is mainly regulated by GPCR kinase 6 (GRK6); thus, silencing of GRK6 expression by siRNA impairs CXCR4-serine 339 phosphorylation and migration of CSCs caused by SCF. In vivo, knockdown of GRK6 impairs the ability of CSCs to migrate into peri-infarcted areas. These results demonstrate that SCF-induced CSC migration is regulated by the transactivation of CXCR4-serine 339 phosphorylation, which is mediated by GRK6.
Microsomal membrane proteome of low grade diffuse astrocytomas: Differentially expressed proteins and candidate surveillance biomarkers
Authors: Polisetty Ravindra Varma , Gautam Poonam , Gupta Manoj Kumar , Sharma Rakesh , Gowda Harsha , Renu Durairaj , Shivakumar Bhadravathi Marigowda , Lakshmikantha Akhila , Mariswamappa Kiran , Ankathi Praveen , Purohit Aniruddh K. , Uppin Megha S. , Sundaram Challa , Sirdeshmukh Ravi
Published: June 2016

Diffuse astrocytoma (DA; WHO grade II) is a low-grade, primary brain neoplasm with high potential of recurrence as higher grade malignant form. We have analyzed differentially expressed membrane proteins from these tumors, using high-resolution mass spectrometry. A total of 2803 proteins were identified, 340 of them differentially expressed with minimum of 2 fold change and based on ≥2 unique peptides. Bioinformatics analysis of this dataset also revealed important molecular networks and pathways relevant to tumorigenesis, mTOR signaling pathway being a major pathway identified. Comparison of 340 differentially expressed proteins with the transcript data from Grade II diffuse astrocytomas reported earlier, revealed about 190 of the proteins correlate in their trends in expression. Considering progressive and recurrent nature of these tumors, we have mapped the differentially expressed proteins for their secretory potential, integrated the resulting list with similar list of proteins from anaplastic astrocytoma (WHO Grade III) tumors and provide a panel of proteins along with their proteotypic peptides, as a resource that would be useful for investigation as circulatory plasma markers for post-treatment surveillance of DA patients.
Transition metal sulfides grown on graphene fibers for wearable asymmetric supercapacitors with high volumetric capacitance and high energy density
Authors: Cai Weihua , Lai Ting , Lai Jianwei , Xie Haoting , Ouyang Liuzhang , Ye Jianshan , Yu Chengzhong
Published: June 2016

Fiber shaped supercapacitors are promising candidates for wearable electronics because they are flexible and light-weight. However, a critical challenge of the widespread application of these energy storage devices is their low cell voltages and low energy densities, resulting in limited run-time of the electronics. Here, we demonstrate a 1.5 V high cell voltage and high volumetric energy density asymmetric fiber supercapacitor in aqueous electrolyte. The lightweight (0.24 g cm−3), highly conductive (39 S cm−1) and mechanically robust (221 MPa) graphene fibers were firstly fabricated and then coated by NiCo2S4 nanoparticles (GF/NiCo2S4) via the solvothermal deposition method. The GF/NiCo2S4 display high volumetric capacitance up to 388 F cm−3 at 2 mV s−1 in a three-electrode cell and 300 F cm−3 at 175.7 mA cm−3 (568 mF cm−2 at 0.5 mA cm−2) in a two-electrode cell. The electrochemical characterizations show 1000% higher capacitance of the GF/NiCo2S4 as compared to that of neat graphene fibers. The fabricated device achieves high energy density up to 12.3 mWh cm−3 with a maximum power density of 1600 mW cm−3, outperforming the thin-film lithium battery. Therefore, these supercapacitors are promising for the next generation flexible and wearable electronic devices.
A synthetic kisspeptin analog that triggers ovulation and advances puberty
Authors: Decourt C. , Robert V. , Anger K. , Galibert M. , Madinier J.-B. , Liu X. , Dardente H. , Lomet D. , Delmas A. F. , Caraty A. , Herbison A. E. , Anderson G. M , Aucagne V. , Beltramo M.
Published: June 2016

The neuropeptide kisspeptin and its receptor, KiSS1R, govern the reproductive timeline of mammals by triggering puberty onset and promoting ovulation by stimulating gonadotrophin-releasing hormone (GnRH) secretion. To overcome the drawback of kisspeptin short half-life we designed kisspeptin analogs combining original modifications, triazole peptidomimetic and albumin binding motif, to reduce proteolytic degradation and to slow down renal clearance, respectively. These analogs showed improved in vitro potency and dramatically enhanced pharmacodynamics. When injected intramuscularly into ewes (15 nmol/ewe) primed with a progestogen, the best analog (compound 6, C6) induced synchronized ovulations in both breeding and non-breeding seasons. Ovulations were fertile as demonstrated by the delivery of lambs at term. C6 was also fully active in both female and male mice but was completely inactive in KiSS1R KO mice. Electrophysiological recordings of GnRH neurons from brain slices of GnRH-GFP mice indicated that C6 exerted a direct excitatory action on GnRH neurons. Finally, in prepubertal female mice daily injections (0.3 nmol/mouse) for five days significantly advanced puberty. C6 ability to trigger ovulation and advance puberty demonstrates that kisspeptin analogs may find application in the management of livestock reproduction and opens new possibilities for the treatment of reproductive disorders in humans.
Hyperlipidemia-associated gene variations and expression patterns revealed by whole-genome and transcriptome sequencing of rabbit models
Authors: Wang Zhen , Zhang Jifeng , Li Hong , Li Junyi , Niimi Manabu , Ding Guohui , Chen Haifeng , Xu Jie , Zhang Hongjiu , Xu Ze , Dai Yulin , Gui Tuantuan , Li Shengdi , Liu Zhi , Wu Sujuan , Cao Mushui , Zhou Lu , Lu Xingyu , Wang Junxia , Yang Jing , Fu Yunhe , Yang Dongshan , Song Jun , Zhu Tianqing , Li Shen , Ning Bo , Wang Ziyun , Koike Tomonari , Shiomi Masashi , Liu Enqi , Chen Luonan , Fan Jianglin , Chen Y. Eugene , Li Yixue
Published: June 2016

The rabbit (Oryctolagus cuniculus) is an important experimental animal for studying human diseases, such as hypercholesterolemia and atherosclerosis. Despite this, genetic information and RNA expression profiling of laboratory rabbits are lacking. Here, we characterized the whole-genome variants of three breeds of the most popular experimental rabbits, New Zealand White (NZW), Japanese White (JW) and Watanabe heritable hyperlipidemic (WHHL) rabbits. Although the genetic diversity of WHHL rabbits was relatively low, they accumulated a large proportion of high-frequency deleterious mutations due to the small population size. Some of the deleterious mutations were associated with the pathophysiology of WHHL rabbits in addition to theLDLRdeficiency. Furthermore, we conducted transcriptome sequencing of different organs of both WHHL and cholesterol-rich diet (Chol)-fed NZW rabbits. We found that gene expression profiles of the two rabbit models were essentially similar in the aorta, even though they exhibited different types of hypercholesterolemia. In contrast, Chol-fed rabbits, but not WHHL rabbits, exhibited pronounced inflammatory responses and abnormal lipid metabolism in the liver. These results provide valuable insights into identifying therapeutic targets of hypercholesterolemia and atherosclerosis with rabbit models.
Development and Evaluation of a Rapid and Sensitive EBOV-RPA Test for Rapid Diagnosis of Ebola Virus Disease
Authors: Yang Mingjuan , Ke Yuehua , Wang Xuesong , Ren Hang , Liu Wei , Lu Huijun , Zhang Wenyi , Liu Shiwei , Chang Guohui , Tian Shuguang , Wang Lihua , Huang Liuyu , Liu Chao , Yang Ruifu , Chen Zeliang
Published: June 2016

Confirming Ebola virus disease (EVD), a deadly infectious disease, requires real-time RT-PCR, which takes up to a few hours to yield results. Therefore, a rapid diagnostic assay is imperative for EVD diagnosis. A rapid nucleic acid test based on recombinase polymerase amplification (EBOV-RPA) was developed to specifically detect the 2014 outbreak strains. The EBOV-RPA assay was evaluated by testing samples from suspected EVD patients in parallel with RT-PCR. An EBOV-RPA, which could be completed in 20 min, was successfully developed. Of 271 patients who tested positive for Ebola virus by RT-PCR, 264 (sensitivity: 97%, 95% CI: 95.5–99.3%) were positive by EBOV-RPA; 101 of 104 patients (specificity: 97%, 95% CI: 93.9–100%) who tested negative by RT-PCR were also negative by EBOV-RPA. The sensitivity values for samples with a Ct value of <34, which accounted for 95.59% of the samples, was 100%. Discordant samples positive by RT-PCR but negative by EBOV-RPA had significantly high Ct values. Results of external quality assessment samples with EBOV-RPA were 100%, consistent with those of RT-PCR. The EBOV-RPA assay showed 97% sensitivity and 97% specificity for all EVD samples tested, making it a rapid and sensitive test for EVD diagnosis.
Pharmacological inhibition of MyD88 homodimerization counteracts renal ischemia reperfusion-induced progressive renal injury in vivo and in vitro
Authors: Zhang Li-Min , Liu Jian-Hua , Xue Cheng-Biao , Li Ming-Qiang , Xing Shuai , Zhang Xue , He Wen-Tao , Jiang Feng-Chao , Lu Xia , Zhou Ping
Published: June 2016

The activation of innate immunity via myeloid differentiation factor 88 (MyD88) contributes to ischemia reperfusion (I/R) induced acute kidney injury (AKI) and chronic kidney injury. However, since there have not yet been any effective therapy, the exact pharmacological role of MyD88 in the prevention and treatment of renal ischemia reperfusion injury (IRI) is not known. We designed a small molecular compound, TJ-M2010-2, which inhibited MyD88 homodimerization. We used an established unilateral I/R mouse model. All mice undergoing 80 min ischemia through uninephrectomy died within five days without intervention. However, treatment with TJ-M2010-2 alone significantly improved the survival rate to 58.3%. Co-treatment of TJ-M2010-2 with the CD154 antagonist increased survival rates up to 100%. Twenty-eight days post-I/R of 60 min ischemia without nephrectomy, TJ-M2010-2 markedly attenuated renal interstitial and inhibited TGF-β1-induced epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells. Furthermore, TJ-M2010-2 remarkably inhibited TLR/MyD88 signaling in vivo and in vitro. In conclusion, our findings highlight the promising clinical potential of MyD88 inhibitor in preventing and treating acute or chronic renal I/R injuries, and the therapeutic functionality of dual-system inhibition strategy in IRI-induced AKI. Moreover, MyD88 inhibition ameliorates renal I/R injury-induced tubular interstitial fibrosis by suppressing EMT.
4-Trifluoromethyl-p-quinols as dielectrophiles: three-component, double nucleophilic addition/aromatization reactions
Authors: Dong Jinhuan , Shi Lou , Pan Ling , Xu Xianxiu , Liu Qun
Published: June 2016

In recent years, numerous methods have emerged for the synthesis of trifluoromethylated arenes based on the late-stage introduction of a trifluoromethyl group onto an aryl ring. In sharp comparison, the synthesis of trifluoromethylated arenes based on the pre-introduction of a trifluoromethyl group onto an “aromatic to be” carbon has rarely been addressed. It has been found that 4-trifluoromethyl-p-quinol silyl ethers, the readily available and relatively stable compounds, can act as dielectrophiles to be applied to multi-component reactions for the synthesis of various trifluoromethylated arenes. Catalyzed by In(OTf)3, 4-trifluoromethyl-p-quinol silyl ethers react with C-, N- and S-nucleophiles, respectively, in a regiospecific 1,2-addition manner to generate the corresponding highly reactive electrophilic intermediates. Further reaction of the in-situ generated electrophiles with a C-nucleophile followed by spontaneous aromatization enables the construction of functionalized trifluoromethyl arenes. This three-component, double nucleophilic addition/aromatization reaction based on the pre-introduction of a trifluoromethyl group onto an “aromatic to be” carbon provides a divergent strategy for the synthesis of trifluoromethylated arenes under mild reaction conditions in a single operation.
Polyamine transporter in Streptococcus pneumoniae is essential for evading early innate immune responses in pneumococcal pneumonia
Authors: Rai Aswathy N. , Thornton Justin A. , Stokes John , Sunesara Imran , Swiatlo Edwin , Nanduri Bindu
Published: June 2016

Streptococcus pneumoniae is the most common bacterial etiology of pneumococcal pneumonia in adults worldwide. Genomic plasticity, antibiotic resistance and extreme capsular antigenic variation complicates the design of effective therapeutic strategies. Polyamines are ubiquitous small cationic molecules necessary for full expression of pneumococcal virulence. Polyamine transport system is an attractive therapeutic target as it is highly conserved across pneumococcal serotypes. In this study, we compared an isogenic deletion strain of S. pneumoniae TIGR4 in polyamine transport operon (ΔpotABCD) with the wild type in a mouse model of pneumococcal pneumonia. Our results show that the wild type persists in mouse lung 24 h post infection while the mutant strain is cleared by host defense mechanisms. We show that intact potABCD is required for survival in the host by providing resistance to neutrophil killing. Comparative proteomics analysis of murine lungs infected with wild type and ΔpotABCD pneumococci identified expression of proteins that could confer protection to wild type strain and help establish infection. We identified ERM complex, PGLYRP1, PTPRC/CD45 and POSTN as new players in the pathogenesis of pneumococcal pneumonia. Additionally, we found that deficiency of polyamine transport leads to up regulation of the polyamine synthesis genes speE and cad in vitro.
Phosphorylation of FEZ1 by Microtubule Affinity Regulating Kinases regulates its function in presynaptic protein trafficking
Authors: Butkevich Eugenia , Härtig Wolfgang , Nikolov Miroslav , Erck Christian , Grosche Jens , Urlaub Henning , Schmidt Christoph F. , Klopfenstein Dieter R. , Chua John Jia En
Published: June 2016

Adapters bind motor proteins to cargoes and therefore play essential roles in Kinesin-1 mediated intracellular transport. The regulatory mechanisms governing adapter functions and the spectrum of cargoes recognized by individual adapters remain poorly defined. Here, we show that cargoes transported by the Kinesin-1 adapter FEZ1 are enriched for presynaptic components and identify that specific phosphorylation of FEZ1 at its serine 58 regulatory site is mediated by microtubule affinity-regulating kinases (MARK/PAR-1). Loss of MARK/PAR-1 impairs axonal transport, with adapter and cargo abnormally co-aggregating in neuronal cell bodies and axons. Presynaptic specializations are markedly reduced and distorted in FEZ1 and MARK/PAR-1 mutants. Strikingly, abnormal co-aggregates of unphosphorylated FEZ1, Kinesin-1 and its putative cargoes are present in brains of transgenic mice modelling aspects of Alzheimer’s disease, a neurodegenerative disorder exhibiting impaired axonal transport and altered MARK activity. Our findings suggest that perturbed FEZ1-mediated synaptic delivery of proteins arising from abnormal signalling potentially contributes to the process of neurodegeneration.
Phosphatidylinositol-3-phosphate is light-regulated and essential for survival in retinal rods
Authors: He Feng , Agosto Melina A. , Anastassov Ivan A. , Tse Dennis Y. , Wu Samuel M. , Wensel Theodore G.
Published: June 2016

Phosphoinositides play important roles in numerous intracellular membrane pathways. Little is known about the regulation or function of these lipids in rod photoreceptor cells, which have highly active membrane dynamics. Using new assays with femtomole sensitivity, we determined that whereas levels of phosphatidylinositol-3,4-bisphosphate and phosphatidylinositol-3,4,5-trisphosphate were below detection limits, phosphatidylinositol-3-phosphate (PI(3)P) levels in rod inner/outer segments increased more than 30-fold after light exposure. This increase was blocked in a rod-specific knockout of the PI-3 kinase Vps34, resulting in failure of endosomal and autophagy-related membranes to fuse with lysosomes, and accumulation of abnormal membrane structures. At early ages, rods displayed normal morphology, rhodopsin trafficking, and light responses, but underwent progressive neurodegeneration with eventual loss of both rods and cones by twelve weeks. The degeneration is considerably faster than in rod knockouts of autophagy genes, indicating defects in endosome recycling or other PI(3)P-dependent membrane trafficking pathways are also essential for rod survival.
Bound States in the Continuum in double layer structures
Authors: Li LiangSheng , Yin Hongcheng
Published: June 2016

We have theoretically investigated the reflectivity spectrums of single- and double-layer photonic crystal slabs and the dielectric multilayer stack. It is shown that light can be perfectly confined in a single-layer photonic crystal slab at a given incident angle by changing the thickness, permittivity or hole radius of the structure. With a tunable double-layer photonic crystal slab, we demonstrate that the occurrence of tunable bound states in the continuum is dependent on the spacing between two slabs. Moreover, by analytically investigating the Drude lossless multilayer stack model, the spacing dependence of bound states in the continuum is characterized as the phase matching condition that illuminates these states can occur at any nonzero incident angles by adjusting the spacing.
Polymorphisms in the XPC gene affect urinary bladder cancer risk: a case-control study, meta-analyses and trial sequential analyses
Authors: Sankhwar Monica , Sankhwar Satya Narayan , Bansal Sandeep Kumar , Gupta Gopal , Rajender Singh
Published: June 2016

Compromised activity of the DNA repair enzymes may raise the risk of a number of cancers. We analyzed polymorphisms in the Xeroderma Pigmentosum, Complementation Group C (XPC) gene for their correlation with urinary bladder cancer. Ala499Val and Lys939Gln polymorphisms were genotyped in 234 urinary bladder cancer cases and 258 control samples. A significant association between Ala499Val polymorphism and bladder cancer was observed (OR = 1.78, CI = 1.19–2.66, p = 0.005); however, Lys939Gln was unrelated (OR = 0.97, CI = 0.65–1.45, P = 0.89). Further analysis revealed that Ala499Val was a significant risk factor only in the presence of smoking (OR = 2.23, CI = 1.28–3.87, p < 0.004) or tobacco chewing (OR = 2.40, CI = 1.43–4.04, p = 0.0008). To further appraise the association, we undertook meta-analyses on seven studies (2893 cases and 3056 controls) on Ala499Val polymorphism and eleven studies (5064 cases and 5208 controls) on Lys939Gln polymorphism. Meta-analyses corroborated the above results, showing strong association of Ala499Val (OR = 1.54, CI = 1.21–1.97, p = 0.001) but not that of Lys939Gln (OR = 1.13, CI = 0.95–1.34, p = 0.171) with urinary bladder cancer risk. In conclusion, XPC Ala499Val substitution increases urinary bladder cancer risk, but Lys939Gln appears to be neutral.
ATAC-seq on biobanked specimens defines a unique chromatin accessibility structure in naïve SLE B cells
Authors: Scharer Christopher D. , Blalock Emily L. , Barwick Benjamin G. , Haines Robert R. , Wei Chungwen , Sanz Ignacio , Boss Jeremy M.
Published: June 2016

Biobanking is a widespread practice for storing biological samples for future studies ranging from genotyping to RNA analysis. However, methods that probe the status of the epigenome are lacking. Here, the framework for applying the Assay for Transposase Accessible Sequencing (ATAC-seq) to biobanked specimens is described and was used to examine the accessibility landscape of naïve B cells from Systemic Lupus Erythematosus (SLE) patients undergoing disease flares. An SLE specific chromatin accessibility signature was identified. Changes in accessibility occurred at loci surrounding genes involved in B cell activation and contained motifs for transcription factors that regulate B cell activation and differentiation. These data provide evidence for an altered epigenetic programming in SLE B cells and identify loci and transcription factor networks that potentially impact disease. The ability to determine the chromatin accessibility landscape and identify cis-regulatory elements has broad application to studies using biorepositories and offers significant advantages to improve the molecular information obtained from biobanked samples.
Lower bound for the spatial extent of localized modes in photonic-crystal waveguides with small random imperfections
Authors: Faggiani Rémi , Baron Alexandre , Zang Xiaorun , Lalouat Loïc , Schulz Sebastian A. , O’Regan Bryan , Vynck Kevin , Cluzel Benoît , de Fornel Frédérique , Krauss Thomas F. , Lalanne Philippe
Published: June 2016

Light localization due to random imperfections in periodic media is paramount in photonics research. The group index is known to be a key parameter for localization near photonic band edges, since small group velocities reinforce light interaction with imperfections. Here, we show that the size of the smallest localized mode that is formed at the band edge of a one-dimensional periodic medium is driven instead by the effective photon mass, i.e. the flatness of the dispersion curve. Our theoretical prediction is supported by numerical simulations, which reveal that photonic-crystal waveguides can exhibit surprisingly small localized modes, much smaller than those observed in Bragg stacks thanks to their larger effective photon mass. This possibility is demonstrated experimentally with a photonic-crystal waveguide fabricated without any intentional disorder, for which near-field measurements allow us to distinctly observe a wavelength-scale localized mode despite the smallness (~1/1000 of a wavelength) of the fabrication imperfections.
Neuronal activity in dorsomedial and dorsolateral striatum under the requirement for temporal credit assignment
Authors: Her Eun Sil , Huh Namjung , Kim Jieun , Jung Min Whan
Published: June 2016

To investigate neural processes underlying temporal credit assignment in the striatum, we recorded neuronal activity in the dorsomedial and dorsolateral striatum (DMS and DLS, respectively) of rats performing a dynamic foraging task in which a choice has to be remembered until its outcome is revealed for correct credit assignment. Choice signals appeared sequentially, initially in the DMS and then in the DLS, and they were combined with action value and reward signals in the DLS when choice outcome was revealed. Unlike in conventional dynamic foraging tasks, neural signals for chosen value were elevated in neither brain structure. These results suggest that dynamics of striatal neural signals related to evaluating choice outcome might differ drastically depending on the requirement for temporal credit assignment. In a behavioral context requiring temporal credit assignment, the DLS, but not the DMS, might be in charge of updating the value of chosen action by integrating choice, action value, and reward signals together.
Topological and packing mode modification for solid-state emission enhancement of bis(perfluorostyryl)furan derivatives
Authors: Faurie Alexandre , Mallet Charlotte , Allain Magali , Skene W. G. , Frère Pierre
Published: June 2016

An unsymmetrical bis(perfluorostyryl)furan was designed for enhancing solid-state emission property by multiplying the type and the quantity of the intermolecular contacts.
Single step synthesized sulfur and nitrogen doped carbon nanodots from whey protein: nanoprobes for longterm cell tracking crossing the barrier of photo-toxicity
Authors: Das Bodhisatwa , Dadhich Prabhash , Pal Pallabi , Dhara Santanu
Published: June 2016

Long-term cell tracking via whey protein derived carbon nanodots.
Live-cell quantification and comparison of mammalian oocyte cytosolic lipid content between species, during development, and in relation to body composition using nonlinear vibrational microscopy
Authors: Jasensky Joshua , Boughton Andrew P. , Khmaladze Alexander , Ding Jun , Zhang Chi , Swain Jason E. , Smith George W. , Chen Zhan , Smith Gary D.
Published: June 2016

Cytosolic lipids participate in the growth, development, and overall health of mammalian oocytes including many roles in cellular homeostasis.
Microwave-assisted extraction and ionic liquid-based dispersive liquid–liquid microextraction followed by HPLC for the determination of trace components in a Langdu preparation
Authors: Li Junmei , Shi Qingwen , Jiang Ye , Gao Jinglin , Li Mengjiao , Ma Haiyan
Published: June 2016

(A) Sample solution; (B) injection of extractant and dispersant into sample solution; (C) vortex-assisted formation of emulsion; (D) phase separation by centrifugation; and (E) collection of high-density extractant.
Particle-based immunochemical separation of methicillin resistant Staphylococcus aureus with indirect electrochemical detection of labeling oligonucleotides
Authors: Cihalova K. , Hegerova D. , Dostalova S. , Jelinkova P. , Krejcova L. , Milosavljevic V. , Krizkova S. , Kopel P. , Adam V.
Published: June 2016

Early detection of antibiotic-resistant bacteria causing inflammation in patients is a key for an appropriate and timely treatment.
Manganese-catalyzed regiospecific sp3C–S bond formation through C–C bond cleavage of cyclobutanols
Authors: Ren Rongguo , Wu Zhen , Zhu Chen
Published: June 2016

A manganese-catalyzed regioselective sp3C–S bond formation through C–C bond cleavage of cyclobutanols is described.
Optical properties of regioregular poly(3-hexylthiophene) aggregates from fully atomistic investigations
Authors: Wang Linjun , Beljonne David
Published: June 2016

We report on a first-principle theoretical investigation of the optical absorption and emission spectra of poly(3-hexylthiophene) (P3HT) aggregates by means of a multiscale all-atom hybrid approach, which combines molecular dynamics simulations, quantum-chemical calculations, and solving of a Frenkel–Holstein model.
Coexistence of resistance switching and negative differential resistance in the α-Fe2O3 nanorod film
Authors: Cai Yunyu , Yuan Qinglin , Ye Yixing , Liu Jun , Liang Changhao
Published: June 2016

The coexistence of resistance switching behaviour and the negative differential resistance phenomenon was presented in the α-Fe2O3 nanorod film that was in situ grown on a fluorine-doped tin oxide glass substrate. The migration of inner defects is revealed to be closely related to the switching behaviours.
Predicting pressure-dependent unimolecular rate constants using variational transition state theory with multidimensional tunneling combined with system-specific quantum RRK theory: a definitive test for fluoroform dissociation
Authors: Bao Junwei Lucas , Zhang Xin , Truhlar Donald G.
Published: June 2016

We show that rate constants for dissociation of fluoroform computed by VTST/SS-QRRK agree excellently with definitive experimental data over a wide pressure and temperature range.
Roles of adsorption sites in electron transfer from CdS quantum dots to molecular catalyst cobaloxime studied by time-resolved spectroscopy
Authors: Ye Yun , Xu Yuxing , Huang Lei , Fan Dayong , Feng Zhaochi , Wang Xiuli , Li Can
Published: June 2016

Electron transfer from CdS quantum dots (QDs) to cobaloxime (Co(dmgH)2pyCl) is demonstrated by transient absorption spectroscopy (TAS), and further confirmed using photoluminescence (PL) techniques.
Metal–organic framework-derived hybrid of Fe3C nanorod-encapsulated, N-doped CNTs on porous carbon sheets for highly efficient oxygen reduction and water oxidation
Authors: Zhao Pingping , Hua Xing , Xu Wei , Luo Wei , Chen Shengli , Cheng Gongzhen
Published: June 2016

A hybrid of Fe3C@CNTs grown on N-doped porous carbon sheets derived from MOF exhibited exceedingly high catalytic activity toward ORR and OER.