bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Cytochrome P450 gene CYP6P12 confers pyrethroid resistance in kdr-free Malaysian populations of the dengue vector Aedes albopictus
Authors: Ishak Intan H. , Riveron Jacob M. , Ibrahim Sulaiman S. , Stott Rob , Longbottom Joshua , Irving Helen , Wondji Charles S. 
Published: April 2016

AbstractControl of Aedes albopictus, major dengue and chikungunya vector, is threatened by growing cases of insecticide resistance. The mechanisms driving this resistance remain poorly characterised. This study investigated the molecular basis of insecticide resistance in Malaysian populations of Ae. albopictus. Microarray-based transcription profiling revealed that metabolic resistance (cytochrome P450 up-regulation) and possibly a reduced penetration mechanism (consistent over-expression of cuticular protein genes) were associated with pyrethroid resistance. CYP6P12 over-expression was strongly associated with pyrethroid resistance whereas CYP6N3 was rather consistently over-expressed across carbamate and DDT resistant populations. Other detoxification genes also up-regulated in permethrin resistant mosquitoes included a glucuronosyltransferase (AAEL014279-RA) and the glutathione-S transferases GSTS1 and GSTT3. Functional analyses further supported that CYP6P12 contributes to pyrethroid resistance in Ae. albopictus as transgenic expression of CYP6P12 in Drosophila was sufficient to confer pyrethroid resistance in these flies. Furthermore, molecular docking simulations predicted CYP6P12 possessing enzymatic activity towards pyrethroids. Patterns of polymorphism suggested early sign of selection acting on CYP6P12 but not on CYP6N3. The major role played by P450 in the absence of kdr mutations suggests that addition of the synergist PBO to pyrethroids could improve the efficacy of this insecticide class and overcome resistance in field populations of Ae. albopictus.
Events in Early Life are Associated with Female Reproductive Ageing: A UK Biobank Study
Authors: Ruth Katherine S. , Perry John R. B. , Henley William E. , Melzer David , Weedon Michael N. , Murray Anna 
Published: April 2016

AbstractThe available oocyte pool is determined before birth, with the majority of oocytes lost before puberty. We hypothesised that events occurring before birth, in childhood or in adolescence (‘early-life risk factors’) could influence the size of the oocyte pool and thus the timing of menopause. We included cross-sectional data from 273,474 women from the UK Biobank, recruited in 2006–2010 from across the UK. We analysed the association of early menopause with events occurring before adulthood in 11,781 cases (menopause aged under 45) and 173,641 controls (menopause/pre-menopausal at ≥45 years), in models controlling for potential confounding variables. Being part of a multiple birth was strongly associated with early menopause (odds ratio = 1.42, confidence interval: 1.11, 1.82, P = 8.0 × 10−9, fully-adjusted model). Earlier age at menarche (odds ratio = 1.03, confidence interval: 1.01, 1.06, P = 2.5 × 10−6) and earlier year of birth were also associated with EM (odds ratio = 1.02, confidence interval: 1.00, 1.04, P = 8.0 × 10−6). We also confirmed previously reported associations with smoking, drinking alcohol, educational level and number of births. We identified an association between multiple births and early menopause, which connects events pre-birth, when the oocyte pool is formed, with reproductive ageing in later life.
Chromatin folding and DNA replication inhibition mediated by a highly antitumor-active tetrazolato-bridged dinuclear platinum(II) complex
Authors: Imai Ryosuke , Komeda Seiji , Shimura Mari , Tamura Sachiko , Matsuyama Satoshi , Nishimura Kohei , Rogge Ryan , Matsunaga Akihiro , Hiratani Ichiro , Takata Hideaki , Uemura Masako , Iida Yutaka , Yoshikawa Yuko , Hansen Jeffrey C. , Yamauchi Kazuto , Kanemaki Masato T. , Maeshima Kazuhiro 
Published: April 2016

AbstractChromatin DNA must be read out for various cellular functions and copied for the next cell division. These processes are targets of many anticancer agents. Platinum-based drugs, such as cisplatin, have been used extensively in cancer chemotherapy. The drug–DNA interaction causes DNA crosslinks and subsequent cytotoxicity. Recently, it was reported that an azolato-bridged dinuclear platinum(II) complex, 5-H-Y, exhibits a different anticancer spectrum from cisplatin. Here, using an interdisciplinary approach, we reveal that the cytotoxic mechanism of 5-H-Y is distinct from that of cisplatin. 5-H-Y inhibits DNA replication and also RNA transcription, arresting cells in the S/G2 phase and are effective against cisplatin-resistant cancer cells. Moreover, it causes much less DNA crosslinking than cisplatin and induces chromatin folding. 5-H-Y will expand the clinical applications for the treatment of chemotherapy-insensitive cancers.
Transcriptional, epigenetic and retroviral signatures identify regulatory regions involved in hematopoietic lineage commitment
Authors: Romano Oriana , Peano Clelia , Tagliazucchi Guidantonio Malagoli , Petiti Luca , Poletti Valentina , Cocchiarella Fabienne , Rizzi Ermanno , Severgnini Marco , Cavazza Alessia , Rossi Claudia , Pagliaro Pasqualepaolo , Ambrosi Alessandro , Ferrari Giuliana , Bicciato Silvio , De Bellis Gianluca , Mavilio Fulvio , Miccio Annarita 
Published: April 2016

AbstractGenome-wide approaches allow investigating the molecular circuitry wiring the genetic and epigenetic programs of human somatic stem cells. Hematopoietic stem/progenitor cells (HSPC) give rise to the different blood cell types; however, the molecular basis of human hematopoietic lineage commitment is poorly characterized. Here, we define the transcriptional and epigenetic profile of human HSPC and early myeloid and erythroid progenitors by a combination of Cap Analysis of Gene Expression (CAGE), ChIP-seq and Moloney leukemia virus (MLV) integration site mapping. Most promoters and transcripts were shared by HSPC and committed progenitors, while enhancers and super-enhancers consistently changed upon differentiation, indicating that lineage commitment is essentially regulated by enhancer elements. A significant fraction of CAGE promoters differentially expressed upon commitment were novel, harbored a chromatin enhancer signature, and may identify promoters and transcribed enhancers driving cell commitment. MLV-targeted genomic regions co-mapped with cell-specific active enhancers and super-enhancers. Expression analyses, together with an enhancer functional assay, indicate that MLV integration can be used to identify bona fide developmentally regulated enhancers. Overall, this study provides an overview of transcriptional and epigenetic changes associated to HSPC lineage commitment, and a novel signature for regulatory elements involved in cell identity.
Miniaturized iPS-Cell-Derived Cardiac Muscles for Physiologically Relevant Drug Response Analyses
Authors: Huebsch Nathaniel , Loskill Peter , Deveshwar Nikhil , Spencer C. Ian , Judge Luke M. , Mandegar Mohammad A. , B. Fox Cade , Mohamed Tamer M.A. , Ma Zhen , Mathur Anurag , Sheehan Alice M. , Truong Annie , Saxton Mike , Yoo Jennie , Srivastava Deepak , Desai Tejal A. , So Po-Lin , Healy Kevin E. , Conklin Bruce R. 
Published: April 2016

AbstractTissue engineering approaches have the potential to increase the physiologic relevance of human iPS-derived cells, such as cardiomyocytes (iPS-CM). However, forming Engineered Heart Muscle (EHM) typically requires >1 million cells per tissue. Existing miniaturization strategies involve complex approaches not amenable to mass production, limiting the ability to use EHM for iPS-based disease modeling and drug screening. Micro-scale cardiospheres are easily produced, but do not facilitate assembly of elongated muscle or direct force measurements. Here we describe an approach that combines features of EHM and cardiospheres: Micro-Heart Muscle (μHM) arrays, in which elongated muscle fibers are formed in an easily fabricated template, with as few as 2,000 iPS-CM per individual tissue. Within μHM, iPS-CM exhibit uniaxial contractility and alignment, robust sarcomere assembly and reduced variability and hypersensitivity in drug responsiveness, compared to monolayers with the same cellular composition. μHM mounted onto standard force measurement apparatus exhibited a robust Frank-Starling response to external stretch and a dose-dependent inotropic response to the β-adrenergic agonist isoproterenol. Based on the ease of fabrication, the potential for mass production and the small number of cells required to form μHM, this system provides a potentially powerful tool to study cardiomyocyte maturation, disease and cardiotoxicology in vitro.
Substantial dust loss of bioavailable phosphorus from agricultural soils
Authors: Katra Itzhak , Gross Avner , Swet Nitzan , Tanner Smadar , Krasnov Helena , Angert Alon 
Published: April 2016

AbstractPhosphorus (P) is an essential element in terrestrial ecosystems. Knowledge on the role of dust in the biogeochemical cycling of phosphorus is very limited with no quantitative information on aeolian (by wind) P fluxes from soils. The aim of this study is to focus on P cycling via dust emissions under common land-use practices in an arid environment by integration of sample analyses and aeolian experiments. The experiments indicate significant P fluxes by PM10 dust due to agricultural land use. Even in a single wind-dust event at moderate velocity (7.0 m s−1), P flux in conventional agricultural fields can reach 1.83 kg km−2, that accumulates to a considerable amount per year at a regional scale. The results highlight a negative yearly balance in P content (up to hundreds kg km−2) in all agricultural soils, and thus more P nutrition is required to maintain efficient yield production. In grazing areas where no P nutrition is applied, the soil degradation process can lead to desertification. Emission of P from soil dust sources has significant implications for soil nutrient resources and management strategies in agricultural regions as well as for loading to the atmosphere and global biogeochemical cycles.
Nanodroplet-Vaporization-Assisted Sonoporation for Highly Effective Delivery of Photothermal Treatment
Authors: Liu Wei-Wen , Liu Shu-Wei , Liou Yu-Ren , Wu Yu-Hsun , Yang Ya-Chuen , Wang Churng-Ren Chris , Li Pai-Chi 
Published: April 2016

AbstractSonoporation refers to the use of ultrasound and acoustic cavitation to temporarily enhance the permeability of cellular membranes so as to enhance the delivery efficiency of therapeutic agents into cells. Microbubble-based ultrasound contrast agents are often used to facilitate these cavitation effects. This study used nanodroplets to significantly enhance the effectiveness of sonoporation relative to using conventional microbubbles. Significant enhancements were demonstrated both in vitro and in vivo by using gold nanorods encapsulated in nanodroplets for implementing plasmonic photothermal therapy. Combined excitation by ultrasound and laser radiation is used to trigger the gold nanodroplets to induce a liquid-to-gas phase change, which induces cavitation effects that are three-to-fivefold stronger than when using conventional microbubbles. Enhanced cavitation also leads to significant enhancement of the sonoporation effects. Our in vivo results show that nanodroplet-vaporization-assisted sonoporation can increase the treatment temperature by more than 10 °C above that achieved by microbubble-based sonoporation.
Fast Flexible Transistors with a Nanotrench Structure
Authors: Seo Jung-Hun , Ling Tao , Gong Shaoqin , Zhou Weidong , Ma Alice L. , Guo L. Jay , Ma Zhenqiang 
Published: April 2016

AbstractThe simplification of fabrication processes that can define very fine patterns for large-area flexible radio-frequency (RF) applications is very desirable because it is generally very challenging to realize submicron scale patterns on flexible substrates. Conventional nanoscale patterning methods, such as e-beam lithography, cannot be easily applied to such applications. On the other hand, recent advances in nanoimprinting lithography (NIL) may enable the fabrication of large-area nanoelectronics, especially flexible RF electronics with finely defined patterns, thereby significantly broadening RF applications. Here we report a generic strategy for fabricating high-performance flexible Si nanomembrane (NM)-based RF thin-film transistors (TFTs), capable of over 100 GHz operation in theory, with NIL patterned deep-submicron-scale channel lengths. A unique 3-dimensional etched-trench-channel configuration was used to allow for TFT fabrication compatible with flexible substrates. Optimal device parameters were obtained through device simulation to understand the underlying device physics and to enhance device controllability. Experimentally, a record-breaking 38 GHz maximum oscillation frequency fmax value has been successfully demonstrated from TFTs with a 2 μm gate length built with flexible Si NM on plastic substrates.
Nitrogen hurdle of host alternation for a polyphagous aphid and the associated changes of endosymbionts
Authors: Liu Yan-Hong , Kang Zhi-Wei , Guo Ya , Zhu Guo-Shuai , Rahman Shah M. Mostafizur , Song Yue , Fan Yong-Liang , Jing Xiangfeng , Liu Tong-Xian 
Published: April 2016

AbstractLow proportion of essential amino acids (EAAs) is one of the barriers for animals to use phloem as a diet. Endosymbionts with EAAs synthesis functions are considered crucial for ameliorating the lack of EAAs in insects’ diets. In this study, we transferred the insects from a cabbage-rearedMyzus persicaepopulation onto 3 new plant species including eggplant, tobacco and spinach. The performance on these plants was evaluated and the dynamics of endosymbionts in relation to this host alternation were recorded. We found that the EAAs ratio in phloem was largely determined by the concentrations of non-essential amino acids and the higher proportion of EAAs seemed to favor the population establishment on new plant species and the growth of primary endosymbionts inside insects, which indicated that nitrogen quality was an important factor for aphids to infest and spread on new plant hosts.
Ablation of the androgen receptor from vascular smooth muscle cells demonstrates a role for testosterone in vascular calcification
Authors: Zhu Dongxing , Hadoke Patrick W. F. , Wu Junxi , Vesey Alex T. , Lerman Daniel. A. , Dweck Marc R. , Newby David E. , Smith Lee B. , MacRae Vicky E. 
Published: April 2016

AbstractVascular calcification powerfully predicts mortality and morbidity from cardiovascular disease. Men have a greater risk of cardiovascular disease, compared to women of a similar age. These gender disparities suggest an influence of sex hormones. Testosterone is the primary and most well-recognised androgen in men. Therefore, we addressed the hypothesis that exogenous androgen treatment induces vascular calcification. Immunohistochemical analysis revealed expression of androgen receptor (AR) in the calcified media of human femoral artery tissue and calcified human valves. Furthermore, in vitro studies revealed increased phosphate (Pi)-induced mouse vascular smooth muscle cell (VSMC) calcification following either testosterone or dihydrotestosterone (DHT) treatment for 9 days. Testosterone and DHT treatment increased tissue non-specific alkaline phosphatase (Alpl) mRNA expression. Testosterone-induced calcification was blunted in VSMC-specific AR-ablated (SM-ARKO) VSMCs compared to WT. Consistent with these data, SM-ARKO VSMCs showed a reduction in Osterix mRNA expression. However, intriguingly, a counter-intuitive increase in Alpl was observed. These novel data demonstrate that androgens play a role in inducing vascular calcification through the AR. Androgen signalling may represent a novel potential therapeutic target for clinical intervention.
Zebrafish Müller glia-derived progenitors are multipotent, exhibit proliferative biases and regenerate excess neurons
Authors: Powell Curtis , Cornblath Eli , Elsaeidi Fairouz , Wan Jin , Goldman Daniel 
Published: April 2016

AbstractUnlike mammals, zebrafish can regenerate a damaged retina. Key to this regenerative response are Müller glia (MG) that respond to injury by reprogramming and adopting retinal stem cell properties. These reprogrammed MG divide to produce a proliferating population of retinal progenitors that migrate to areas of retinal damage and regenerate lost neurons. Previous studies have suggested that MG-derived progenitors may be biased to produce that are lost with injury. Here we investigated MG multipotency using injury paradigms that target different retinal nuclear layers for cell ablation. Our data indicate that regardless of which nuclear layer was damaged, MG respond by generating multipotent progenitors that migrate to all nuclear layers and differentiate into layer-specific cell types, suggesting that MG-derived progenitors in the injured retina are intrinsically multipotent. However, our analysis of progenitor proliferation reveals a proliferative advantage in nuclear layers where neurons were ablated. This suggests that feedback inhibition from surviving neurons may skew neuronal regeneration towards ablated cell types.
Resveratrol ameliorates renal injury in spontaneously hypertensive rats by inhibiting renal micro-inflammation
Authors: Xue Hai-Yan , Yuan Li , Cao Ying-Jie , Fan Ya-Ping , Chen Xiao-Lan , Huang Xin-Zhong 
Published: April 2016

Micro-inflammation plays an important role in the pathogenesis of spontaneously hypertensive rat (SHR). In the present study, we investigated the therapeutic potential of resveratrol (RSV), a polyphenol with anti-fibrosis activity in hypertensive renal damage model. In SHR renal damage model, RSV treatment blunted the increase in urine albumin excretion, urinary β2-microglobulin (β2-MG), attenuated the decrease in creatinine clearance rate (CCR). The glomerular sclerosis index (1.54±0.33 compared with 0.36±0.07) and tubulointerstitial fibrosis (1.57±0.31 compared with 0.19±0.04) were significantly higher in SHRs compared with Wistar Kyoto rats (WKYs), which were significantly lower by RSV treatment. The increases in mesangium accumulation and the expression of renal collagen type I (Col I), fibronectin (Fn), plasminogen activator inhibitor-1 (PAI-1) and transforming growth factor-β1 (TGF-β1) in SHR were also reduced by RSV treatment. Nuclear factor κB (NF-κB) expression was increased in the cytoplasm and nuclei of the SHR kidneys, which was significantly decreased by RSV treatment. Furthermore, the protein level of IκB-α significantly decreased in the kidneys of the SHR when compared with the WKYs. RSV treatment partially restored the decreased IκB-α level. In SHR kidney, increased expression of interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein 1 (MCP-1) were observed. These changes were attenuated by RSV treatment. No changes in blood pressure were detected between SHR group and SHR + RSV group. Taken together, the present study demonstrated that RSV treatment may significantly attenuate renal damage in the SHR model of chronic kidney disease (CKD). The renal protective effect is associated with inhibition of IL-6, ICAM-1 and MCP-1 expression via the regulation of the nuclear translocation of NF-κB, which suggesting that micro-inflammation may be a potential therapeutic target of hypertensive renal damage.
The first EGF domain of coagulation factor IX attenuates cell adhesion and induces apoptosis
Authors: Ishikawa Tomomi , Kitano Hisataka , Mamiya Atsushi , Kokubun Shinichiro , Hidai Chiaki 
Published: April 2016

Coagulation factor IX (FIX) is an essential plasma protein for blood coagulation. The first epidermal growth factor (EGF) motif of FIX (EGF-F9) has been reported to attenuate cell adhesion to the extracellular matrix (ECM). The purpose of the present study was to determine the effects of this motif on cell adhesion and apoptosis. Treatment with a recombinant EGF-F9 attenuated cell adhesion to the ECM within 10 min. De-adhesion assays with native FIX recombinant FIX deletion mutant proteins suggested that the de-adhesion activity of EGF-F9 requires the same process of FIX activation as that which occurs for coagulation activity. The recombinant EGF-F9 increased lactate dehydrogenase (LDH) activity release into the medium and increased the number of cells stained with annexin V and activated caspase-3, by 8.8- and 2.7-fold respectively, indicating that EGF-F9 induced apoptosis. Activated caspase-3 increased very rapidly after only 5 min of administration of recombinant EGF-F9. Treatment with EGF-F9 increased the level of phosphorylated p38 mitogen-activated protein kinase (MAPK), but not that of phosphorylated MAPK 44/42 or c-Jun N-terminal kinase (JNK). Inhibitors of caspase-3 suppressed the release of LDH. Caspase-3 inhibitors also suppressed the attenuation of cell adhesion and phosphorylation of p38 MAPK by EGF-F9. Our data indicated that EGF-F9 activated signals for apoptosis and induced de-adhesion in a caspase-3 dependent manner.
A Prekindergarten Curriculum Supplement for Enhancing Mainstream American English Knowledge in Nonmainstream American English Speakers
Authors: Edwards Jan R. , Rosin Peggy 
Published: April 2016

Purpose
The purpose of this study was to evaluate the efficacy of a curriculum supplement designed to enhance awareness of Mainstream American English (MAE) in African American English- (AAE-) speaking prekindergarten children.

Method
Children in 2 Head Start classrooms participated in the study. The experimental classroom received the Talking and Learning for Kindergarten program (Edwards, Rosin, Gross, & Chen, 2013), which used contrastive analysis to highlight morphological, phonological, and pragmatic differences between MAE and AAE. The control classroom received the Kindness Curriculum (Flook, Goldberg, Pinger, & Davidson, 2014), which was designed to promote mindfulness and emotional self-regulation. The amount of instruction was the same across the 2 programs. Both classrooms participated in pre- and posttest assessments.

Results
Children in the experimental classroom, but not the control classroom, showed significant improvement in 3 norm-referenced measures of phonological awareness and in an experimental measure that evaluated comprehension of words that are ambiguous in AAE, but unambiguous in MAE, because of morphological and phonological differences between the 2 dialects.

Conclusion
Although more research needs to be done on the efficacy of the Talking and Learning for Kindergarten program, these results suggest that it is possible to enhance AAE-speaking children's awareness of MAE prior to kindergarten entry.

Supplemental Material

https://doi.org/10.23641/asha.6170288